{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T19:45:04Z","timestamp":1774899904253,"version":"3.50.1"},"reference-count":186,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2022.09644.BD"],"award-info":[{"award-number":["2022.09644.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>The tumor microenvironment (TME) comprises neoplastic and stromal cells, and extracellular matrix elements, all engaging in a complex interplay that ultimately dictates tumorigenesis, cancer progression, and therapeutic response. While extensive research on the TME has been conducted in human oncology, data on its veterinary counterpart, particularly in feline mammary tumors (FMTs), are still scarce. In this review, we explore current understanding of feline mammary carcinoma (FMC) microenvironment, focusing on tumor necrosis, fibrosis, angiogenesis, adipose tissue tumor-associated inflammation, extracellular vesicles, and epithelial\u2013mesenchymal transition (EMT) and their prognostic implications. In FMC, remodeling of collagen fibers, cancer-associated fibroblasts (CAFs), regulatory T cells (Tregs) and elevated serum leptin have been associated with poor prognosis, whereas stromal cytotoxic T cells correlate with more favorable outcomes. By contrast, findings on necrosis and pro-angiogenic factors remain inconsistent, and research on extracellular vesicles (EVs) is still in its early stages. This review presents insights from human breast cancer (HBC) that further support and elucidate the potential relevance of these TME components. As FMCs are highly aggressive tumors, a deeper understanding of their microenvironment could not only improve prognostic accuracy but also uncover novel therapeutic targets. Furthermore, due to their similarities, FMCs offer a potential valuable spontaneous model for HBC, particularly for the aggressive triple-negative phenotypes.<\/jats:p>","DOI":"10.3390\/vetsci12100959","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:04:52Z","timestamp":1759925092000},"page":"959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value\u2014A Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-4425","authenticated-orcid":false,"given":"Joana","family":"Rodrigues-Jesus","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, ICBAS-UP, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associated Laboratory for Green Chemistry (LAQV), REQUIMTE, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5770-8454","authenticated-orcid":false,"given":"Ana","family":"Canadas-Sousa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, ICBAS-UP, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associated Laboratory for Green Chemistry (LAQV), REQUIMTE, University of Porto, 4050-313 Porto, Portugal"},{"name":"Vasco da Gama Research Centre (CIVG), Department of Veterinary Sciences, Vasco da Gama University School (EUVG), 3020-210 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-1619","authenticated-orcid":false,"given":"Hugo","family":"Vilhena","sequence":"additional","affiliation":[{"name":"Vasco da Gama Research Centre (CIVG), Department of Veterinary Sciences, Vasco da Gama University School (EUVG), 3020-210 Coimbra, Portugal"},{"name":"Department of Veterinary Clinics, School of Medicine and Biomedical Sciences, ICBAS-UP, University of Porto, 4050-313 Porto, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), University of Tr\u00e1s-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Associate Laboratory of Animal and Veterinary Sciences, AL4AnimaLS, 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8845-794X","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Dias-Pereira","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, ICBAS-UP, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associated Laboratory for Green Chemistry (LAQV), REQUIMTE, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(00)49915-0","article-title":"Distribution of Secondary Growths in Cancer of the Breast","volume":"133","author":"Paget","year":"1889","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12307-009-0025-8","article-title":"The Tumor Microenvironment: The Making of a Paradigm","volume":"2","author":"Witz","year":"2009","journal-title":"Cancer Microenviron."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.immuni.2019.06.025","article-title":"Inflammation and Cancer: Triggers, Mechanisms and Consequences","volume":"51","author":"Greten","year":"2019","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1158\/0008-5472.CAN-18-3962","article-title":"The Tumor Microenvironment Innately Modulates Cancer Progression","volume":"79","author":"Hinshaw","year":"2019","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.immuni.2019.06.021","article-title":"Pas de Deux: Control of Anti-Tumor Immunity by Cancer-Associated Inflammation","volume":"51","author":"Shalapour","year":"2019","journal-title":"Immunity"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Roma-Rodrigues, C., Mendes, R., Baptista, P.V., and Fernandes, A.R. (2019). Targeting Tumor Microenvironment for Cancer Therapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040840"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tsai, M.-J., Chang, W.-A., Huang, M.-S., and Kuo, P.-L. (2014). Tumor Microenvironment: A New Treatment Target for Cancer. ISRN Biochem., 2014.","DOI":"10.1155\/2014\/351959"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Caliari, D., Zappulli, V., Rasotto, R., Cardazzo, B., Frassineti, F., Goldschmidt, M.H., and Castagnaro, M. (2014). Triple-Negative Vimentin-Positive Heterogeneous Feline Mammary Carcinomas as a Potential Comparative Model for Breast Cancer. BMC Vet. Res., 10.","DOI":"10.1186\/s12917-014-0185-8"},{"key":"ref_9","first-page":"111","article-title":"Cats, Cancer and Comparative Oncology","volume":"2","author":"Cannon","year":"2015","journal-title":"Vet. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/rda.14408","article-title":"Mammary Carcinoma: Comparative Oncology between Small Animals and Humans\u2014New Therapeutic Tools","volume":"58","author":"Nguyen","year":"2023","journal-title":"Reprod. Domest. Anim."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gameiro, A., Urbano, A.C., and Ferreira, F. (2021). Emerging Biomarkers and Targeted Therapies in Feline Mammary Carcinoma. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.625147"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nascimento, C., and Ferreira, F. (2021). Tumor Microenvironment of Human Breast Cancer, and Feline Mammary Carcinoma as a Potential Study Model. Biochim. Biophys. Acta Rev. Cancer, 1876.","DOI":"10.1016\/j.bbcan.2021.188587"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.breast.2016.02.016","article-title":"Molecular Based Subtyping of Feline Mammary Carcinomas and Clinicopathological Characterization","volume":"27","author":"Soares","year":"2016","journal-title":"Breast"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/vco.12800","article-title":"Comparative Gene Expression Study Highlights Molecular Similarities between Triple Negative Breast Cancer Tumours and Feline Mammary Carcinomas","volume":"20","author":"Sommerville","year":"2022","journal-title":"Vet. Comp. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wiese, D.A., Thaiwong, T., Yuzbasiyan-Gurkan, V., and Kiupel, M. (2013). Feline Mammary Basal-like Adenocarcinomas: A Potential Model for Human Triple-Negative Breast Cancer (TNBC) with Basal-like Subtype. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-403"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1017\/S0022029905001263","article-title":"Feline Mammary Tumours in Comparative Oncology","volume":"72","author":"Zappulli","year":"2005","journal-title":"J. Dairy Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/cbin.11137","article-title":"Cell Death: A Review of the Major Forms of Apoptosis, Necrosis and Autophagy","volume":"43","year":"2019","journal-title":"Cell Biol. Int."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Miller, M.A., and Zachary, J.F. (2017). General Pathology\u2014Chapter 1: Mechanisms and Morphology of Cellular Injury, Adaptation, and Death. Pathologic Basis of Veterinary Disease, Elsevier.","DOI":"10.1016\/B978-0-323-35775-3.00001-1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2217\/fon.11.99","article-title":"The Prognostic Value of Histological Tumor Necrosis in Solid Organ Malignant Disease: A Systematic Review","volume":"7","author":"Richards","year":"2011","journal-title":"Future Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and Cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5881","DOI":"10.21873\/anticanres.15408","article-title":"Targeting Production of Reactive Oxygen Species as an Anticancer Strategy","volume":"41","author":"Kourti","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1111\/cas.15068","article-title":"Reactive Oxygen Species in Cancer: Current Findings and Future Directions","volume":"112","author":"Nakamura","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yee, P.P., and Li, W. (2021). Tumor Necrosis: A Synergistic Consequence of Metabolic Stress and Inflammation. BioEssays, 43.","DOI":"10.1002\/bies.202100029"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"152652","DOI":"10.1016\/j.prp.2019.152652","article-title":"Programmed Necrosis and Its Role in Management of Breast Cancer","volume":"215","author":"Thakur","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1177\/0300985821999831","article-title":"Review of Histological Grading Systems in Veterinary Medicine","volume":"58","author":"Avallone","year":"2021","journal-title":"Vet. Pathol."},{"key":"ref_26","unstructured":"Moore, F.M., Williams, B., Bertram, C.A., Donovan, T.A., Klopfleisch, R., Meuten, D.J., and Santos, R.L. (2023, August 09). Tumor Necrosis Guideline, Version 1.1. Veterinary Cancer Guidelines and Protocols. Available online: http:\/\/vetcancerprotocols.org."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chen, B., Lin, S.J.-H., Li, W.-T., Chang, H.-W., Pang, V.F., Chu, P.-Y., Lee, C.-C., Nakayama, H., Wu, C.-H., and Jeng, C.-R. (2020). Expression of HIF-1\u03b1 and VEGF in Feline Mammary Gland Carcinomas: Association with Pathological Characteristics and Clinical Outcomes. BMC Vet. Res., 16.","DOI":"10.1186\/s12917-020-02338-y"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1177\/0300985819846870","article-title":"Feline Invasive Mammary Carcinomas: Prognostic Value of Histological Grading","volume":"56","author":"Dagher","year":"2019","journal-title":"Vet. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/1097-0142(197507)36:1<1::AID-CNCR2820360102>3.0.CO;2-4","article-title":"The Pathology of Invasive Breast Cancer. A Syllabus Derived from Findings of the National Surgical Adjuvant Breast Project (Protocol No. 4)","volume":"36","author":"Fisher","year":"1975","journal-title":"Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0046-8177(78)80133-6","article-title":"Pathological Findings from the National Surgical Adjuvant Breast Project (Protocol No. 4). IV. Significance of Tumor Necrosis","volume":"9","author":"Fisher","year":"1978","journal-title":"Hum. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gameiro, A., Nascimento, C., Correia, J., and Ferreira, F. (2021). HER2-Targeted Immunotherapy and Combined Protocols Showed Promising Antiproliferative Effects in Feline Mammary Carcinoma Cell-Based Models. Cancers, 13.","DOI":"10.3390\/cancers13092007"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gameiro, A., Nascimento, C., Urbano, A.C., Correia, J., and Ferreira, F. (2021). Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.625147"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/sj.bjc.6690158","article-title":"Necrosis Correlates with High Vascular Density and Focal Macrophage Infiltration in Invasive Carcinoma of the Breast","volume":"79","author":"Leek","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nascimento, C., Gameiro, A., Correia, J., Ferreira, J., and Ferreira, F. (2022). The Landscape of Tumor-Infiltrating Immune Cells in Feline Mammary Carcinoma: Pathological and Clinical Implications. Cells, 11.","DOI":"10.3390\/cells11162578"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rodrigues-Jesus, J., Canadas-Sousa, A., Santos, M., Oliveira, P., Figueira, A.C., Marrinhas, C., Petrucci, G.N., Greg\u00f3rio, H., Tinoco, F., and Goulart, A. (2024). Level of Necrosis in Feline Mammary Tumors: How to Quantify, Why and for What Purpose?. Animals, 14.","DOI":"10.3390\/ani14223280"},{"key":"ref_36","unstructured":"Zappulli, V., Pe\u00f1a, L., Rasotto, R., Goldschmidt, M.H., Gama, A., Scruggs, J.L., and Kiupel, M. (2019). Surgical Pathology of Tumors of Domestic Animals\u2014Volume 2: Mammary Tumors, Davis-Thompson DVM Foundation. [3rd ed.]."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1177\/0300985814543198","article-title":"Prognostic Value of Histologic Grading for Feline Mammary Carcinoma: A Retrospective Survival Analysis","volume":"52","author":"Mills","year":"2015","journal-title":"Vet. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tvjl.2009.10.030","article-title":"Grade Is an Independent Prognostic Factor for Feline Mammary Carcinomas: A Clinicopathological and Survival Analysis","volume":"187","author":"Seixas","year":"2011","journal-title":"Vet. J."},{"key":"ref_39","first-page":"709","article-title":"Prognostic Factors in Feline Mammary Carcinoma","volume":"70","author":"Weijer","year":"1983","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000227001","article-title":"Histological Assessment of the Prognostic Factors in Female Breast Cancer","volume":"49","author":"Aaltomaa","year":"1992","journal-title":"Oncology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000227472","article-title":"Prognostic Significance of Necrosis, Elastosis, Fibrosis and Inflammatory Cell Reaction in Operable Breast Cancer","volume":"52","author":"Carlomagno","year":"1995","journal-title":"Oncology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/00000478-197803000-00005","article-title":"Relationship of Necrosis and Tumor Border to Lymph Node Metastases and 10-Year Survival in Carcinoma of the Breast","volume":"2","author":"Carter","year":"1978","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1200\/JCO.1993.11.10.1929","article-title":"Tumor Necrosis Is a Prognostic Predictor for Early Recurrence and Death in Lymph Node-Positive Breast Cancer: A 10-Year Follow-up Study of 728 Eastern Cooperative Oncology Group Patients","volume":"11","author":"Gilchrist","year":"1993","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1354\/vp.39-6-690","article-title":"Correlation of Vascular Endothelial Growth Factor Expression to Overall Survival in Feline Invasive Mammary Carcinomas","volume":"39","author":"Millanta","year":"2002","journal-title":"Vet. Pathol."},{"key":"ref_45","first-page":"1003","article-title":"Evaluation of Prognostic Factors and Survival Rates in Malignant Feline Mammary Gland Neoplasms","volume":"18","author":"Damasceno","year":"2015","journal-title":"J. Feline Med. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Rosen, S., Brisson, B.K., Durham, A.C., Munroe, C.M., McNeill, C.J., Stefanovski, D., S\u00f8renmo, K.U., and Volk, S.W. (2020). Intratumoral Collagen Signatures Predict Clinical Outcomes in Feline Mammary Carcinoma. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0236516"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"598","DOI":"10.21873\/invivo.13478","article-title":"Immunohistochemical Expression and Prognostic Value of COX-2 and Alpha-Smooth Muscle Actin-Positive Cancer-Associated Fibroblasts in Feline Mammary Cancer","volume":"38","author":"Petrucci","year":"2024","journal-title":"In Vivo"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7185","DOI":"10.1158\/0008-5472.CAN-14-2598","article-title":"Mechanisms of Hypoxia-Mediated Immune Escape in Cancer","volume":"74","author":"Barsoum","year":"2014","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1002\/med.21771","article-title":"The Role of Hypoxia-Inducible Factor 1 in Tumor Immune Evasion","volume":"41","author":"You","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_50","unstructured":"Kumar, V., Abbas, A.K., and Aster, J.C. (2021). Chapter 7: Neoplasia. Robbins & Cotran Pathologic Basis of Disease, Elsevier."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/sj.leu.2404402","article-title":"The History of the Angiogenic Switch Concept","volume":"21","author":"Ribatti","year":"2007","journal-title":"Leukemia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.semcancer.2009.05.003","article-title":"The Angiogenic Switch in Carcinogenesis","volume":"19","author":"Baeriswyl","year":"2009","journal-title":"Semin. Cancer Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrc1093","article-title":"Tumorigenesis and the Angiogenic Switch","volume":"3","author":"Bergers","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Newkirk, K.M., Brannick, E.M., and Kusewitt, D.F. (2017). General Pathology\u2014Chapter 6: Neoplasia and Tumor Biology. Pathologic Basis of Veterinary Disease, Elsevier.","DOI":"10.1016\/B978-0-323-35775-3.00006-0"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1007\/s00018-019-03351-7","article-title":"Tumor Angiogenesis: Causes, Consequences, Challenges and Opportunities","volume":"77","author":"Lugano","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.rvsc.2006.01.007","article-title":"The Role of Vascular Endothelial Growth Factor and Its Receptor Flk-1\/KDR in Promoting Tumour Angiogenesis in Feline and Canine Mammary Carcinomas: A Preliminary Study of Autocrine and Paracrine Loops","volume":"81","author":"Millanta","year":"2006","journal-title":"Res. Vet. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Nascimento, C., Gameiro, A., Ferreira, J., Correia, J., and Ferreira, F. (2021). Diagnostic Value of VEGF-A, VEGFR-1 and VEGFR-2 in Feline Mammary Carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13010117"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.tvjl.2011.08.032","article-title":"Expression of NOS and VEGF in Feline Mammary Tumours and Their Correlation with Angiogenesis","volume":"192","author":"Islam","year":"2012","journal-title":"Vet. J."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sarli, G., Sassi, F., Brunetti, B., Rizzo, A., Diracca, L., and Benazzi, C. (2007). Lymphatic Vessels Assessment in Feline Mammary Tumours. BMC Cancer, 7.","DOI":"10.1186\/1471-2407-7-7"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1242\/dmm.004077","article-title":"Remodeling and Homeostasis of the Extracellular Matrix: Implications for Fibrotic Diseases and Cancer","volume":"4","author":"Cox","year":"2011","journal-title":"Dis. Model. Mech."},{"key":"ref_62","unstructured":"Kumar, V., Abbas, A.K., and Aster, J.C. (2021). Chapter 3: Inflammation and Repair. Robbins & Cotran Pathologic Basis of Disease, Elsevier."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ackermann, M.R. (2017). General Pathology\u2014Chapter 3: Inflammation and Healing. Pathologic Basis of Veterinary Disease, Elsevier.","DOI":"10.1016\/B978-0-323-35775-3.00003-5"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.trsl.2019.02.006","article-title":"The Double Edge Sword of Fibrosis in Cancer","volume":"209","author":"Chandler","year":"2019","journal-title":"Transl. Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Piersma, B., Hayward, M.-K., and Weaver, V.M. (2020). Fibrosis and Cancer: A Strained Relationship. Biochim. Biophys. Acta BBA Rev. Cancer, 1873.","DOI":"10.1016\/j.bbcan.2020.188356"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrc2544","article-title":"A Tense Situation: Forcing Tumour Progression","volume":"9","author":"Butcher","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1152\/physiolgenomics.00158.2013","article-title":"The Wound Healing, Chronic Fibrosis, and Cancer Progression Triad","volume":"46","author":"Rybinski","year":"2014","journal-title":"Physiol. Genomics"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Brassart-Pasco, S., Br\u00e9zillon, S., Brassart, B., Ramont, L., Oudart, J.-B., and Monboisse, J.C. (2020). Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00397"},{"key":"ref_69","first-page":"1","article-title":"Extracellular Matrix and Its Therapeutic Potential for Cancer Treatment","volume":"6","author":"Huang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1158\/1055-9965.EPI-06-0034","article-title":"Breast Density and Parenchymal Patterns as Markers of Breast Cancer Risk: A Meta-Analysis","volume":"15","author":"McCormack","year":"2006","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gkretsi, V., and Stylianopoulos, T. (2018). Cell Adhesion and Matrix Stiffness: Coordinating Cancer Cell Invasion and Metastasis. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00145"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ceb.2018.09.002","article-title":"Cancer Associated Fibroblasts: Is the Force the Path to the Dark Side?","volume":"56","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Ishihara, S., and Haga, H. (2022). Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors. Cancers, 14.","DOI":"10.3390\/cancers14041049"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s00262-017-2003-1","article-title":"Tumor-Associated Fibrosis as a Regulator of Tumor Immunity and Response to Immunotherapy","volume":"66","author":"Jiang","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1039\/c5ib00040h","article-title":"Human Breast Cancer Invasion and Aggression Correlates with ECM Stiffening and Immune Cell Infiltration","volume":"7","author":"Acerbi","year":"2015","journal-title":"Integr. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/1097-0215(20010120)95:1<67::AID-IJC1012>3.0.CO;2-U","article-title":"Stromal Expression of Fibroblast Activation Protein\/Seprase, a Cell Membrane Serine Proteinase and Gelatinase, Is Associated with Longer Survival in Patients with Invasive Ductal Carcinoma of Breast","volume":"95","author":"Ariga","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.prp.2017.06.016","article-title":"CD61+ and CAF+ Were Found to Be Good Prognosis Factors for Invasive Breast Cancer Patients","volume":"213","author":"Cai","year":"2017","journal-title":"Pathol. Res. Pract."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Martinez, L.M., Labovsky, V., de Luj\u00e1n Calcagno, M., Davies, K.M., Garcia Rivello, H., Bianchi, M.S., Wernicke, A., Fern\u00e1ndez Vallone, V.B., and Chasseing, N.A. (2015). CD105 Expression on CD34-Negative Spindle-Shaped Stromal Cells of Primary Tumor Is an Unfavorable Prognostic Marker in Early Breast Cancer Patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121421"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10549-016-3929-2","article-title":"Expression of Cancer-Associated Fibroblast-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma","volume":"159","author":"Park","year":"2016","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"334","DOI":"10.2353\/ajpath.2009.081030","article-title":"Prognostic Significance of Stromal Platelet-Derived Growth Factor \u03b2-Receptor Expression in Human Breast Cancer","volume":"175","author":"Paulsson","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1111\/j.1365-2559.2011.04060.x","article-title":"Podoplanin Expression by Cancer-Associated Fibroblasts Predicts Poor Outcome in Invasive Ductal Breast Carcinoma","volume":"59","author":"Pula","year":"2011","journal-title":"Histopathology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s10549-012-1984-x","article-title":"Podoplanin-Expressing Cancer-Associated Fibroblasts Are Associated with Poor Prognosis in Invasive Breast Cancer","volume":"134","author":"Schoppmann","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_83","first-page":"2917","article-title":"Occurence of Stromal Myofibroblasts in the Invasive Ductal Breast Cancer Tissue Is an Unfavourable Prognostic Factor","volume":"27","author":"Surowiak","year":"2007","journal-title":"Anticancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s12282-010-0234-5","article-title":"Role of Stromal Myofibroblasts in Invasive Breast Cancer: Stromal Expression of Alpha-Smooth Muscle Actin Correlates with Worse Clinical Outcome","volume":"19","author":"Yamashita","year":"2012","journal-title":"Breast Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.yexmp.2017.02.012","article-title":"Tenascin C Is a Prognostic Determinant and Potential Cancer-Associated Fibroblasts Marker for Breast Ductal Carcinoma","volume":"102","author":"Yang","year":"2017","journal-title":"Exp. Mol. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s10549-010-0855-6","article-title":"Tumor\u2013Stroma Ratio in the Primary Tumor Is a Prognostic Factor in Early Breast Cancer Patients, Especially in Triple-Negative Carcinoma Patients","volume":"125","author":"Putter","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s10549-017-4445-8","article-title":"The Prognostic Value of the Tumour-Stroma Ratio in Primary Operable Invasive Cancer of the Breast: A Validation Study","volume":"166","author":"Roeke","year":"2017","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s10549-017-4617-6","article-title":"Prognostic Value of Tumor-Stroma Ratio Combined with the Immune Status of Tumors in Invasive Breast Carcinoma","volume":"168","author":"Vangangelt","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9050631","DOI":"10.1155\/2020\/9050631","article-title":"Prognostic Significance of the Tumor-Stromal Ratio in Invasive Breast Cancer and a Proposal of a New Ts-TNM Staging System","volume":"2020","author":"Xu","year":"2020","journal-title":"J. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s10549-022-06587-3","article-title":"Standardization of the Tumor-Stroma Ratio Scoring Method for Breast Cancer Research","volume":"193","author":"Hagenaars","year":"2022","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.rvsc.2018.06.012","article-title":"Relationship between the Inflammatory Tumor Microenvironment and Different Histologic Types of Canine Mammary Tumors","volume":"119","author":"Nunes","year":"2018","journal-title":"Res. Vet. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Case, A., Brisson, B.K., Durham, A.C., Rosen, S., Monslow, J., Buza, E., Salah, P., Gillem, J., Ruthel, G., and Veluvolu, S. (2017). Identification of Prognostic Collagen Signatures and Potential Therapeutic Stromal Targets in Canine Mammary Gland Carcinoma. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180448"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.jcpa.2017.03.006","article-title":"Obesity and Associated Comorbidities in People and Companion Animals: A One Health Perspective","volume":"156","author":"Chandler","year":"2017","journal-title":"J. Comp. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1098612X241285519","DOI":"10.1177\/1098612X241285519","article-title":"Overweight and Obesity in Domestic Cats: Epidemiological Risk Factors and Associated Pathologies","volume":"26","author":"Saavedra","year":"2024","journal-title":"J. Feline Med. Surg."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Marshall, T., Chen, J., and Viloria-Petit, A.M. (2023). Adipocyte-Derived Adipokines and Other Obesity-Associated Molecules in Feline Mammary Cancer. Biomedicines, 11.","DOI":"10.3390\/biomedicines11082309"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Estevez, L., Gonz\u00e1lez-Mart\u00ednez, S., and Moreno-Bueno, G. (2021). The Leptin Axis and Its Association With the Adaptive Immune System in Breast Cancer. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.784823"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Lagarde, C.B., Thapa, K., Cullen, N.M., Hawes, M.L., Salim, K., Benz, M.C., Dietrich, S.R., Burow, B.E., Bunnell, B.A., and Martin, E.C. (2024). Obesity and Leptin in Breast Cancer Angiogenesis. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1465727"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"215616","DOI":"10.1016\/j.canlet.2022.215616","article-title":"Contribution of Adipocytes in the Tumor Microenvironment to Breast Cancer Metabolism","volume":"534","author":"Lyu","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/bmj.1.5022.779","article-title":"Cancer\u2014A Biological Approach","volume":"1","author":"Burnet","year":"1957","journal-title":"Br. Med. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1093\/oxfordjournals.bmb.a070310","article-title":"Immunological Factors In The Process Of Carcinogenesis","volume":"20","author":"Burnet","year":"1964","journal-title":"Br. Med. Bull."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/ni1102-991","article-title":"Cancer Immunoediting: From Immunosurveillance to Tumor Escape","volume":"3","author":"Dunn","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1146\/annurev.immunol.22.012703.104803","article-title":"The Three Es of Cancer Immunoediting","volume":"22","author":"Dunn","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Danforth, D.N. (2021). The Role of Chronic Inflammation in the Development of Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13153918"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s10549-014-2896-8","article-title":"Immune Cell Quantitation in Normal Breast Tissue Lobules with and without Lobulitis","volume":"144","author":"Degnim","year":"2014","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1158\/1078-0432.CCR-16-2026","article-title":"Alterations in the Immune Cell Composition in Premalignant Breast Tissue That Precede Breast Cancer Development","volume":"23","author":"Degnim","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1093\/jnci\/49.6.1697","article-title":"Feline Malignant Mammary Tumors. I. Morphology and Biology: Some Comparisons with Human and Canine Mammary Carcinomas","volume":"49","author":"Weijer","year":"1972","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Chocteau, F., Boulay, M.-M., Besnard, F., Valeau, G., Loussouarn, D., and Nguyen, F. (2019). Proposal for a Histological Staging System of Mammary Carcinomas in Dogs and Cats. Part 2: Feline Mammary Carcinomas. Front. Vet. Sci., 6.","DOI":"10.3389\/fvets.2019.00387"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Dagher, E., Abadie, J., Loussouarn, D., Fanuel, D., Campone, M., and Nguyen, F. (2019). Bcl-2 Expression and Prognostic Significance in Feline Invasive Mammary Carcinomas: A Retrospective Observational Study. BMC Vet. Res., 15.","DOI":"10.1186\/s12917-018-1772-x"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/vco.12987","article-title":"Distribution of Inflammatory Infiltrate in Feline Mammary Lesions: Relationship With Clinicopathological Features","volume":"22","author":"Oliveira","year":"2024","journal-title":"Vet. Comp. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Dagher, E., Simbault, L., Abadie, J., Loussouarn, D., Campone, M., and Nguyen, F. (2020). Identification of an Immune-Suppressed Subtype of Feline Triple-Negative Basal-like Invasive Mammary Carcinomas, Spontaneous Models of Breast Cancer. Tumour Biol., 42.","DOI":"10.1177\/1010428319901052"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1177\/0300985820908792","article-title":"Biphasic Feline Mammary Carcinomas Including Carcinoma and Malignant Myoepithelioma","volume":"57","author":"Sammarco","year":"2020","journal-title":"Vet. Pathol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Urbano, A.C., Nascimento, C., Soares, M., Correia, J., and Ferreira, F. (2020). Clinical Relevance of the Serum CTLA-4 in Cats with Mammary Carcinoma. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-60860-3"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"106870","DOI":"10.1016\/j.imlet.2024.106870","article-title":"The Th1\/Th2 Paradigm: A Misrepresentation of Helper T Cell Plasticity","volume":"268","author":"Rogozynski","year":"2024","journal-title":"Immunol. Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/bcr1746","article-title":"Inflammation and Breast Cancer. Balancing Immune Response: Crosstalk between Adaptive and Innate Immune Cells during Breast Cancer Progression","volume":"9","author":"DeNardo","year":"2007","journal-title":"Breast Cancer Res. BCR"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.trecan.2021.06.007","article-title":"Immunity beyond Cancer Cells: Perspective from Tumor Tissue","volume":"7","author":"Gao","year":"2021","journal-title":"Trends Cancer"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12943-017-0721-9","article-title":"Tumor-Related Interleukins: Old Validated Targets for New Anti-Cancer Drug Development","volume":"16","author":"Setrerrahmane","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"300","DOI":"10.32007\/jfacmedbagdad.5131130","article-title":"IL-2 and IL-4 Serum Levels in Breast Cancer","volume":"51","year":"2009","journal-title":"J. Fac. Med. Baghdad"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.21873\/anticanres.11093","article-title":"Determination of Interleukin-4, -5, -6, -8 and -13 in Serum of Patients with Breast Cancer Before Treatment and Its Correlation to Circulating Tumor Cells","volume":"36","author":"Vilsmaier","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Paccagnella, M., Abbona, A., Michelotti, A., Geuna, E., Ruatta, F., Landucci, E., Denaro, N., Vanella, P., Lo Nigro, C., and Galizia, D. (2022). Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression. Vaccines, 10.","DOI":"10.3390\/vaccines10010078"},{"key":"ref_120","first-page":"88","article-title":"Plasma Biomarkers Profile of Female Dogs with Mammary Carcinoma and Its Association with Clinical and Pathological Features","volume":"14","author":"Soares","year":"2013","journal-title":"Vet. Comp. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Kawaguchi, K., Sakurai, M., Yamamoto, Y., Suzuki, E., Tsuda, M., Kataoka, T.R., Hirata, M., Nishie, M., Nojiri, T., and Kumazoe, M. (2019). Alteration of Specific Cytokine Expression Patterns in Patients with Breast Cancer. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-39476-9"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e1537691","DOI":"10.1080\/2162402X.2018.1537691","article-title":"Noninvasive Profiling of Serum Cytokines in Breast Cancer Patients and Clinicopathological Characteristics","volume":"8","author":"Jabeen","year":"2019","journal-title":"OncoImmunology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/his.13695","article-title":"Heterogeneity of Tumour-Infiltrating Lymphocytes in Breast Cancer and Its Prognostic Significance","volume":"73","author":"Althobiti","year":"2018","journal-title":"Histopathology"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Millar, E., Browne, L., Slapetova, I., Shang, F., Ren, Y., Bradshaw, R., Ann Brauer, H., O\u2019Toole, S., Beretov, J., and Whan, R. (2020). TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up. Cancers, 12.","DOI":"10.3390\/cancers12092365"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4103\/0019-509X.118744","article-title":"Presence of CD3+ Tumor Infiltrating Lymphocytes Is Significantly Associated with Good Prognosis in Infiltrating Ductal Carcinoma of Breast","volume":"50","author":"Rathore","year":"2013","journal-title":"Indian J. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s10549-011-1620-1","article-title":"The Prognostic Significance of B Lymphocytes in Invasive Carcinoma of the Breast","volume":"132","author":"Mahmoud","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1038\/bjc.2013.493","article-title":"The Relationship between Lymphocyte Subsets and Clinico-Pathological Determinants of Survival in Patients with Primary Operable Invasive Ductal Breast Cancer","volume":"109","author":"Mohammed","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4048\/jbc.2014.17.1.8","article-title":"Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer","volume":"17","author":"Kim","year":"2014","journal-title":"J. Breast Cancer"},{"key":"ref_129","first-page":"1107","article-title":"Prognostic Significance of CD8+ T Lymphocytes in Breast Cancer Depends upon Both Oestrogen Receptor Status and Histological Grade","volume":"58","author":"Baker","year":"2011","journal-title":"Histopathology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1097\/COC.0b013e3182467d90","article-title":"Tumor-Infiltrating Lymphocytes, Tumor Characteristics, and Recurrence in Patients with Early Breast Cancer","volume":"36","author":"Kim","year":"2013","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1093\/annonc\/mdu191","article-title":"Association between CD8+ T-Cell Infiltration and Breast Cancer Survival in 12 439 Patients","volume":"25","author":"Ali","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Chen, Z., Chen, X., Zhou, E., Chen, G., Qian, K., Wu, X., Miao, X., and Tang, Z. (2014). Intratumoral CD8+ Cytotoxic Lymphocyte Is a Favorable Prognostic Marker in Node-Negative Breast Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095475"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5373","DOI":"10.1200\/JCO.2006.05.9584","article-title":"Quantification of Regulatory T Cells Enables the Identification of High-Risk Breast Cancer Patients and Those at Risk of Late Relapse","volume":"24","author":"Bates","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4549676","DOI":"10.1155\/2016\/4549676","article-title":"Macrophages: Regulators of the Inflammatory Microenvironment during Mammary Gland Development and Breast Cancer","volume":"2016","author":"Brady","year":"2016","journal-title":"Mediators Inflamm."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Munir, M.T., Kay, M.K., Kang, M.H., Rahman, M.M., Al-Harrasi, A., Choudhury, M., Moustaid-Moussa, N., Hussain, F., and Rahman, S.M. (2021). Tumor-Associated Macrophages as Multifaceted Regulators of Breast Tumor Growth. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126526"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Van Dalen, F.J., Van Stevendaal, M.H.M.E., Fennemann, F.L., Verdoes, M., and Ilina, O. (2019). Molecular Repolarisation of Tumour-Associated Macrophages. Molecules, 24.","DOI":"10.3390\/molecules24010009"},{"key":"ref_137","first-page":"6656","article-title":"The Role of Tumor-Associated Macrophages in Breast Carcinoma Invasion and Metastasis","volume":"8","author":"Yang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Gwak, J.M., Jang, M.H., Kim, D.I., Seo, A.N., and Park, S.Y. (2015). Prognostic Value of Tumor-Associated Macrophages According to Histologic Locations and Hormone Receptor Status in Breast Cancer. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125728"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"38","DOI":"10.4048\/jbc.2019.22.e5","article-title":"Tumor-Associated Macrophages as Potential Prognostic Biomarkers of Invasive Breast Cancer","volume":"22","author":"Jeong","year":"2019","journal-title":"J. Breast Cancer"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13058-015-0621-0","article-title":"Human Breast Cancer Cells Educate Macrophages toward the M2 Activation Status","volume":"17","author":"Sousa","year":"2015","journal-title":"Breast Cancer Res."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Medrek, C., Pont\u00e9n, F., Jirstr\u00f6m, K., and Leandersson, K. (2012). The Presence of Tumor Associated Macrophages in Tumor Stroma as a Prognostic Marker for Breast Cancer Patients. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-306"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e6663","DOI":"10.1097\/MD.0000000000006663","article-title":"Jagged1 Modulated Tumor-Associated Macrophage Differentiation Predicts Poor Prognosis in Patients with Invasive Micropapillary Carcinoma of the Breast","volume":"96","author":"Liu","year":"2017","journal-title":"Medicine"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Salemme, V., Centonze, G., Cavallo, F., Defilippi, P., and Conti, L. (2021). The Crosstalk Between Tumor Cells and the Immune Microenvironment in Breast Cancer: Implications for Immunotherapy. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.610303"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Zhang, C., Liu, W., Yang, P., Lin, R., Pu, L., and Zhang, H. (2025). Dual Roles of Innate Immune Cells and Cytokines in Shaping the Breast Cancer Microenvironment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1654947"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e37654","DOI":"10.1097\/MD.0000000000037654","article-title":"Exploring Neutrophil Functionality in Breast Cancer Progression: A Review","volume":"103","author":"Obeagu","year":"2024","journal-title":"Medicine"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"118699","DOI":"10.1016\/j.lfs.2020.118699","article-title":"Tumor-Associated Neutrophils as New Players in Immunosuppressive Process of the Tumor Microenvironment in Breast Cancer","volume":"264","author":"Hajizadeh","year":"2021","journal-title":"Life Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e047957","DOI":"10.1136\/bmjopen-2020-047957","article-title":"Role of Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy: A Meta-Analysis","volume":"11","author":"Zhou","year":"2021","journal-title":"BMJ Open"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/vco.12686","article-title":"Neutrophil-to-Lymphocyte Ratio Is an Independent Prognostic Marker for Feline Mammary Carcinomas","volume":"19","author":"Petrucci","year":"2021","journal-title":"Vet. Comp. Oncol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.rvsc.2020.10.015","article-title":"Prognostic Utility of Preoperative Neutrophil-Lymphocyte Ratio in Cats with Malignant Mammary Tumors","volume":"135","author":"Naito","year":"2021","journal-title":"Res. Vet. Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.clbc.2021.08.010","article-title":"Controversial Role of Mast Cells in Breast Cancer Tumor Progression and Angiogenesis","volume":"21","author":"Ribatti","year":"2021","journal-title":"Clin. Breast Cancer"},{"key":"ref_151","first-page":"1131","article-title":"Antitumorogenic Effect of Mast Cells: Insights from an Experimentally-Induced Mammary Carcinoma Model in Rats and Feline and Canine Mammary Tumors","volume":"44","author":"Yavas","year":"2024","journal-title":"Pak. Vet. J."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Gupta, Y.H., Khanom, A., and Acton, S.E. (2022). Control of Dendritic Cell Function Within the Tumour Microenvironment. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.733800"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nature21349","article-title":"Elements of Cancer Immunity and the Cancer\u2013Immune Set Point","volume":"541","author":"Chen","year":"2017","journal-title":"Nature"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Tiwari, A., Oravecz, T., Dillon, L.A., Italiano, A., Audoly, L., Fridman, W.H., and Clifton, G.T. (2023). Towards a Consensus Definition of Immune Exclusion in Cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1084887"},{"key":"ref_155","first-page":"1","article-title":"Cold and Hot Tumors: From Molecular Mechanisms to Targeted Therapy","volume":"9","author":"Wu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_156","first-page":"963","article-title":"T-Lymphocytic Infiltrate in Canine Mammary Tumours: Clinic and Prognostic Implications","volume":"25","author":"Carvalho","year":"2011","journal-title":"In Vivo"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Vilela, T., Valente, S., Correia, J., and Ferreira, F. (2024). Advances in Immunotherapy for Breast Cancer and Feline Mammary Carcinoma: From Molecular Basis to Novel Therapeutic Targets. Biochim. Biophys. Acta Rev. Cancer, 1879.","DOI":"10.1016\/j.bbcan.2024.189144"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Nascimento, C., Urbano, A.C., Gameiro, A., Ferreira, J., Correia, J., and Ferreira, F. (2020). Serum PD-1\/PD-L1 Levels, Tumor Expression and PD-L1 Somatic Mutations in HER2-Positive and Triple Negative Normal-Like Feline Mammary Carcinoma Subtypes. Cancers, 12.","DOI":"10.1101\/2020.04.25.061655"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Gameiro, A., Nascimento, C., Correia, J., and Ferreira, F. (2021). VISTA Is a Diagnostic Biomarker and Immunotherapy Target of Aggressive Feline Mammary Carcinoma Subtypes. Cancers, 13.","DOI":"10.3390\/cancers13215559"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Valente, S., Nascimento, C., Gameiro, A., Ferreira, J., Correia, J., and Ferreira, F. (2023). TIM-3 Is a Potential Immune Checkpoint Target in Cats with Mammary Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15020384"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Maekawa, N., Konnai, S., Asano, Y., Otsuka, T., Aoki, E., Takeuchi, H., Kato, Y., Kaneko, M.K., Yamada, S., and Kagawa, Y. (2023). Molecular Characterization of Feline Immune Checkpoint Molecules and Establishment of PD-L1 Immunohistochemistry for Feline Tumors. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0281143"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Franco, M., Seixas, F., dos Anjos Pires, M., Alves, A., Santos, A., Marrinhas, C., Vilhena, H., Santos, J., Fa\u00edsca, P., and Dias-Pereira, P. (2025). PD-1, PD-L1, and PD-L2 Expression as Predictive Markers in Rare Feline Mammary Tumors. Vet. Sci., 12.","DOI":"10.3390\/vetsci12080731"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Diomaiuto, E., Principe, V., De Luca, A., Laperuta, F., Alterisio, C., and Di Loria, A. (2021). Exosomes in Dogs and Cats: An Innovative Approach to Neoplastic and Non-Neoplastic Diseases. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080766"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Sullivan, R., Maresh, G., Zhang, X., Salomon, C., Hooper, J., Margolin, D., and Li, L. (2017). The Emerging Roles of Extracellular Vesicles As Communication Vehicles within the Tumor Microenvironment and Beyond. Front. Endocrinol., 8.","DOI":"10.3389\/fendo.2017.00194"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Howard, J., Wyse, C., Argyle, D., Quinn, C., Kelly, P., and McCann, A. (2020). Exosomes as Biomarkers of Human and Feline Mammary Tumours; A Comparative Medicine Approach to Unravelling the Aggressiveness of TNBC. Biochim. Biophys. Acta Rev. Cancer, 1874.","DOI":"10.1016\/j.bbcan.2020.188431"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41392-024-01937-7","article-title":"Pre-Metastatic Niche: Formation, Characteristics and Therapeutic Implication","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/vco.12405","article-title":"Preliminary Investigation of Extracellular Vesicles in Mammary Cancer of Dogs and Cats: Identification and Characterization","volume":"16","author":"Sammarco","year":"2018","journal-title":"Vet. Comp. Oncol."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Howard, J., Browne, J., Bollard, S., Peters, S., Sweeney, C., Wynne, K., Potter, S., McCann, A., and Kelly, P. (2023). The Protein and miRNA Profile of Plasma Extracellular Vesicles (EVs) Can Distinguish Feline Mammary Adenocarcinoma Patients from Healthy Feline Controls. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-36110-7"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s42826-023-00180-5","article-title":"Feline Mammary Carcinoma-Derived Extracellular Vesicle Promotes Liver Metastasis via Sphingosine Kinase-1-Mediated Premetastatic Niche Formation","volume":"39","author":"Chang","year":"2023","journal-title":"Lab. Anim. Res."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Chang, Y.-C., Chuang, H.-L., Yin, J.-H., Liao, J.-W., Chen, T.-H., and Wang, Y.-C. (2019). Significance of Sphingosine Kinase 1 Expression in Feline Mammary Tumors. BMC Vet. Res., 15.","DOI":"10.1186\/s12917-019-1883-z"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41580-020-0237-9","article-title":"Guidelines and Definitions for Research on Epithelial\u2013Mesenchymal Transition","volume":"21","author":"Yang","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41580-018-0080-4","article-title":"New Insights into the Mechanisms of Epithelial\u2013Mesenchymal Transition and Implications for Cancer","volume":"20","author":"Dongre","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Sammarco, A., Gomiero, C., Beffagna, G., Cavicchioli, L., Ferro, S., Michieletto, S., Orvieto, E., Patruno, M., and Zappulli, V. (2023). Epithelial-to-Mesenchymal Transition and Phenotypic Marker Evaluation in Human, Canine, and Feline Mammary Gland Tumors. Animals, 13.","DOI":"10.3390\/ani13050878"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tvjl.2011.01.011","article-title":"Sequence Variation and mRNA Expression of the TWIST1 Gene in Cats with Mammary Hyperplasia and Neoplasia","volume":"191","author":"Baptista","year":"2012","journal-title":"Vet. J."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1177\/0300985812436744","article-title":"Reduced Expression of E-Cadherin and \u03b2-Catenin and High Expression of Basal Cytokeratins in Feline Mammary Carcinomas with Regional Metastasis","volume":"49","author":"Buendia","year":"2012","journal-title":"Vet. Pathol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0021-9975(05)80095-7","article-title":"Immunohistochemical Distribution Pattern of Intermediate Filament Proteins and Muscle Actin in Feline and Human Mammary Carcinomas","volume":"111","author":"Bautista","year":"1994","journal-title":"J. Comp. Pathol."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Granados-Soler, J.L., Junginger, J., Hewicker-Trautwein, M., Bornemann-Kolatzki, K., Beck, J., Brenig, B., Betz, D., Schille, J.T., Murua Escobar, H., and Nolte, I. (2018). TiHo-0906: A New Feline Mammary Cancer Cell Line with Molecular, Morphological, and Immunocytological Characteristics of Epithelial to Mesenchymal Transition. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31682-1"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"687424","DOI":"10.1155\/2012\/687424","article-title":"P-Cadherin Expression in Feline Mammary Tissues","volume":"2012","author":"Figueira","year":"2012","journal-title":"Vet. Med. Int."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Figueira, A.C., Gomes, C., de Oliveira, J.T., Vilhena, H., Carvalheira, J., de Matos, A.J.F., Pereira, P.D., and G\u00e4rtner, F. (2014). Aberrant P-Cadherin Expression Is Associated to Aggressive Feline Mammary Carcinomas. BMC Vet. Res., 10.","DOI":"10.1186\/s12917-014-0270-z"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1136\/vr.153.10.297","article-title":"Expression of E-Cadherin in Normal, Hyperplastic and Neoplastic Feline Mammary Tissue","volume":"153","year":"2003","journal-title":"Vet. Rec."},{"key":"ref_181","first-page":"3361","article-title":"Characterization of \u03b1-, \u03b2- and P120-Catenin Expression in Feline Mammary Tissues and Their Relation with E- and P-Cadherin","volume":"35","author":"Figueira","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jcpa.2012.02.004","article-title":"Immunohistochemical Expression of E-Cadherin and \u03b2-Catenin in Feline Mammary Tumours","volume":"147","author":"Zappulli","year":"2012","journal-title":"J. Comp. Pathol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1292\/jvms.21-0021","article-title":"Immunocytochemical Evaluation of Epithelial-Mesenchymal Transition in Epithelial Tumors of Dogs and Cats","volume":"83","author":"Furusawa","year":"2021","journal-title":"J. Vet. Med. Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"100197","DOI":"10.1016\/j.modpat.2023.100197","article-title":"Multiplex Immunohistochemistry and Immunofluorescence: A Practical Update for Pathologists","volume":"36","author":"Harms","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13073-022-01075-1","article-title":"An Introduction to Spatial Transcriptomics for Biomedical Research","volume":"14","author":"Williams","year":"2022","journal-title":"Genome Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s12943-024-02040-9","article-title":"Advances in Spatial Transcriptomics and Its Applications in Cancer Research","volume":"23","author":"Jin","year":"2024","journal-title":"Mol. 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