{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:16:14Z","timestamp":1787030174267,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Horizon 2020 research and innovation programme under ITN Marie Sk\u0142odowska-Curie grant agreement","doi-asserted-by":"publisher","award":["956544"],"award-info":[{"award-number":["956544"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Horizon 2020 research and innovation programme under ITN Marie Sk\u0142odowska-Curie grant agreement","doi-asserted-by":"publisher","award":["PID2022\u2013136735OB-I00"],"award-info":[{"award-number":["PID2022\u2013136735OB-I00"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigacio\u00f3n (AEI, Spain) project","doi-asserted-by":"publisher","award":["956544"],"award-info":[{"award-number":["956544"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigacio\u00f3n (AEI, Spain) project","doi-asserted-by":"publisher","award":["PID2022\u2013136735OB-I00"],"award-info":[{"award-number":["PID2022\u2013136735OB-I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Nucleic acid-based anticancer vaccines are becoming a very active field in the fight against cancer. Here, our goal was to generate an oral DNA vaccine targeting the angiogenic peptide, proadrenomedullin N-terminal 20 peptide (PAMP). Methods: An expression plasmid (PcPAMP) was generated by fusing the tetanus toxin epitopes P2 and P30 to the mouse PAMP sequence to counteract self-tolerance, and the empty plasmid was used as a negative control (PcNeg). The plasmids were introduced into Salmonella typhimurium bacteria that were then transformed into bacterial ghosts. C57BL\/6J mice were orally immunized with the ghosts five times at 2-week intervals. Then, B16-F10 melanoma cells were injected into the tail vein to generate lung metastases. Furthermore, na\u00efve CD4+ T cells were exposed to PAMP, and their secretome was analyzed by proximity extension assays. Results: Significant levels of anti-PAMP immunoglobulins were detected in the blood of PcPAMP-vaccinated mice and their levels of spleen CD8+ T cells were significantly higher than in those treated with PcNeg, indicating that self-tolerance was effectively broken. Although the number and size of lung metastases was similar between both experimental groups, there was a significant reduction in intratumoral angiogenesis and in cancer cell proliferation index in the PcPAMP group. Furthermore, these animals showed an intense infiltration of lymphocytes, including regulatory T cells, and M2-like macrophages into the metastases, that was not evident in the PcNeg group. In addition, PAMP induced upregulation of IL1\u03b2, IL6, IL7, IL12, IL27, TNF\u03b1, and FGF21, and downregulation of IL16 in na\u00efve CD4+ T cells. Conclusions: Although the vaccine was not effective in reducing tumor growth, new proliferative and immune functions have been described for PAMP. These new functions include induction of melanoma proliferation and modulation of lymphocyte and macrophage tumor infiltration dynamics.<\/jats:p>","DOI":"10.3390\/vaccines13060586","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T08:07:58Z","timestamp":1748592478000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A DNA Vaccine Against Proadrenomedullin N-Terminal 20 Peptide (PAMP) Reduces Angiogenesis and Increases Lymphocyte and Macrophage Infiltration but Has No Effect on Tumor Burden in a Mouse Model of Lung Metastasis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-1571","authenticated-orcid":false,"given":"Tom Kalathil","family":"Raju","sequence":"first","affiliation":[{"name":"Angiogenesis Unit, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srdan","family":"Tadic","sequence":"additional","affiliation":[{"name":"Angiogenesis Unit, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5960-8569","authenticated-orcid":false,"given":"Pablo","family":"Garrido","sequence":"additional","affiliation":[{"name":"Angiogenesis Unit, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-6613","authenticated-orcid":false,"given":"Laura","family":"Ochoa-Callejero","sequence":"additional","affiliation":[{"name":"Angiogenesis Unit, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-4930","authenticated-orcid":false,"given":"Judit","family":"Narro-\u00cd\u00f1iguez","sequence":"additional","affiliation":[{"name":"Angiogenesis Unit, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4391-5537","authenticated-orcid":false,"given":"Josune","family":"Garc\u00eda-Sanmart\u00edn","sequence":"additional","affiliation":[{"name":"Angiogenesis Unit, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-4044","authenticated-orcid":false,"given":"Alfredo","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Angiogenesis Unit, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.phrs.2018.08.023","article-title":"Therapeutic implication of vascular endothelial growth factor receptor-1 (VEGFR-1) targeting in cancer cells and tumor microenvironment by competitive and non-competitive inhibitors","volume":"136","author":"Lacal","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2174\/0118715206356712241202112641","article-title":"Advances in VEGFR Inhibitors: A Comprehensive Review of Novel Anticancer Agents","volume":"25","author":"Jha","year":"2025","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"re12","DOI":"10.1126\/stke.3062005re12","article-title":"Integration of oxygen signaling at the consensus HRE","volume":"2005","author":"Wenger","year":"2005","journal-title":"Sci. STKE"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.canlet.2005.04.008","article-title":"A new family of angiogenic factors","volume":"236","author":"Martinez","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.canlet.2020.05.015","article-title":"Hypoxia: Turning vessels into vassals of cancer immunotolerance","volume":"487","author":"Schito","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Okamoto, T., Usuda, H., Tanaka, T., Wada, K., and Shimaoka, M. (2019). The Functional Implications of Endothelial Gap Junctions and Cellular Mechanics in Vascular Angiogenesis. Cancers, 11.","DOI":"10.3390\/cancers11020237"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0074-7696(02)21010-4","article-title":"Cell and molecular biology of the multifunctional peptide, adrenomedullin","volume":"221","author":"Lopez","year":"2002","journal-title":"Int. Rev. Cytol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/bip.20418","article-title":"NMR conformational analysis of proadrenomedullin N-terminal 20 peptide, a proangiogenic factor involved in tumor growth","volume":"81","author":"Lucyk","year":"2006","journal-title":"Biopolymers"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jemt.10052","article-title":"Adrenomedullin and PAMP: Discovery, structures, and cardiovascular functions","volume":"57","author":"Kitamura","year":"2002","journal-title":"Microsc. Res. Tech."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"L241","DOI":"10.1016\/0024-3205(95)02117-2","article-title":"Comparison of bronchodilator responses to adrenomedullin and proadrenomedullin N-terminal 20 peptide","volume":"57","author":"Kanazawa","year":"1995","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1161\/01.HYP.30.5.1009","article-title":"A newly identified peptide, proadrenomedullin N-terminal 20 peptide, induces hypotensive action via pertussis toxin-sensitive mechanisms","volume":"30","author":"Shimosawa","year":"1997","journal-title":"Hypertension"},{"key":"ref_13","first-page":"1263","article-title":"Proadrenomedullin-derived peptides as autocrine-paracrine regulators of cell growth","volume":"16","author":"Belloni","year":"2001","journal-title":"Histol. Histopathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1161\/01.HYP.33.5.1185","article-title":"Proadrenomedullin N-terminal 20 peptide (PAMP), acting through PAMP(12-20)-sensitive receptors, inhibits Ca2+-dependent, agonist-stimulated secretion of human adrenal glands","volume":"33","author":"Belloni","year":"1999","journal-title":"Hypertension"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.regpep.2005.02.001","article-title":"Effect of adrenomedullin and proadrenomedullin N-terminal 20 peptide on sugar transport in the rat intestine","volume":"129","author":"Lostao","year":"2005","journal-title":"Regul. Pept."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1210\/en.2006-0105","article-title":"Molecular evolution of proadrenomedullin N-terminal 20 peptide (PAMP): Evidence for gene co-option","volume":"147","author":"Martinez","year":"2006","journal-title":"Endocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6489","DOI":"10.1158\/0008-5472.CAN-04-0103","article-title":"Proadrenomedullin NH2-terminal 20 peptide is a potent angiogenic factor, and its inhibition results in reduction of tumor growth","volume":"64","author":"Zudaire","year":"2004","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/30666","article-title":"RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor","volume":"393","author":"McLatchie","year":"1998","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.bbrc.2005.03.088","article-title":"Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides","volume":"330","author":"Kamohara","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1021\/acsptsci.1c00006","article-title":"Proadrenomedullin N-Terminal 20 Peptides (PAMPs) Are Agonists of the Chemokine Scavenger Receptor ACKR3\/CXCR7","volume":"4","author":"Meyrath","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1210\/en.2007-1763","article-title":"Intracellular proadrenomedullin-derived peptides decorate the microtubules and contribute to cytoskeleton function","volume":"149","author":"Sackett","year":"2008","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1210\/en.2011-1685","article-title":"Proadrenomedullin N-terminal 20 peptide increases kinesin\u2019s velocity both in vitro and in vivo","volume":"153","author":"Larrayoz","year":"2012","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.2174\/13892037113149990059","article-title":"Is the cytoskeleton an intracellular receptor for adrenomedullin and PAMP?","volume":"14","author":"Larrayoz","year":"2013","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Saleh, R.O., Ibrahim, F.M., Pallathadka, H., Kaur, I., Ahmad, I., Ali, S.H.J., Redhee, A.H., Ghildiyal, P., Jawad, M.A., and Alsaadi, S.B. (2024). Nucleic acid vaccines-based therapy for triple-negative breast cancer: A new paradigm in tumor immunotherapy arena. Cell Biochem. Funct., 42.","DOI":"10.1002\/cbf.3992"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13073-024-01388-3","article-title":"Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients","volume":"16","author":"Zhang","year":"2024","journal-title":"Genome Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kumar, A., Dixit, S., Srinivasan, K.M.D., and Vincent, P.M.D.R. (2024). Personalized cancer vaccine design using AI-powered technologies. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1357217"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kozak, M., and Hu, J. (2024). DNA Vaccines: Their Formulations, Engineering and Delivery. Vaccines, 12.","DOI":"10.3390\/vaccines12010071"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tadic, S., and Martinez, A. (2024). Nucleic acid cancer vaccines targeting tumor related angiogenesis. Could mRNA vaccines constitute a game changer?. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1433185"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1001217","DOI":"10.1080\/2162402X.2014.1001217","article-title":"Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial","volume":"4","author":"Hohmann","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1303584","DOI":"10.1080\/2162402X.2017.1303584","article-title":"A phase 1 trial extension to assess immunologic efficacy and safety of prime-boost vaccination with VXM01, an oral T cell vaccine against VEGFR2, in patients with advanced pancreatic cancer","volume":"7","author":"Hohmann","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"vi9","DOI":"10.1093\/neuonc\/noy148.030","article-title":"ATIM-35, VXM01 phase 1 study in patients with progressive glioblastoma. Final results","volume":"20","author":"Wick","year":"2018","journal-title":"Neuro Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1200\/JCO.2020.38.15_suppl.3001","article-title":"Oral DNA vaccination targeting VEGFR2 combined with anti-PDL1 avelumab in patients with progressive glioblastoma: Safety run-in results\u2014NCT03750071","volume":"38","author":"Wick","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/nbt858","article-title":"High-level generation of polyclonal antibodies by genetic immunization","volume":"21","author":"Chambers","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.molimm.2003.08.006","article-title":"Optimization of codon pair use within the (GGGGS)3 linker sequence results in enhanced protein expression","volume":"40","author":"Trinh","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jsps.2017.12.006","article-title":"A novel protocol for bacterial ghosts\u2019 preparation using tween 80","volume":"26","author":"Rabea","year":"2018","journal-title":"Saudi Pharm. J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ochoa-Callejero, L., Pozo-Rodrigalvarez, A., Martinez-Murillo, R., and Martinez, A. (2016). Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage. Sci. Rep., 6.","DOI":"10.1038\/srep33495"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1210\/endo.138.1.4881","article-title":"Expression of adrenomedullin and its receptor during embryogenesis suggests autocrine or paracrine modes of action","volume":"138","author":"Montuenga","year":"1997","journal-title":"Endocrinology"},{"key":"ref_38","unstructured":"Tadic, S., Ochoa-Callejero, L., Narro-\u00cd\u00f1iguez, J., Garcia-Sanmartin, J., and Martinez, A. (2025). An RNA vaccine against adrenomedullin reduces angiogenesis and tumor burden in a syngeneic metastatic melanoma mouse model. Front. Immunol., 16."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/CJI.0000000000000040","article-title":"Enhancement of DNA vaccine potency against legumain","volume":"37","author":"Smahel","year":"2014","journal-title":"J. Immunother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e136773","DOI":"10.1172\/jci.insight.136773","article-title":"Ovarian granulosa cell tumor characterization identifies FOXL2 as an immunotherapeutic target","volume":"5","author":"Pierini","year":"2020","journal-title":"JCI Insight"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2404316","DOI":"10.1002\/adhm.202404316","article-title":"Neoantigen-Displaying Protein Nanoparticles as a Therapeutic Cancer Vaccine Against Melanoma","volume":"14","author":"Kim","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/ijc.21838","article-title":"Antiangiogenic combination tumor therapy blocking \u03b1v-integrins and VEGF-receptor-2 increases therapeutic effects in vivo","volume":"119","author":"Strieth","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1186\/s12967-014-0339-2","article-title":"Adrenomedullin and tumour microenvironment","volume":"12","author":"Larrayoz","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e20211628","DOI":"10.1084\/jem.20211628","article-title":"Suppression of CCL2 angiocrine function by adrenomedullin promotes tumor growth","volume":"220","author":"Nakayama","year":"2023","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/S0014-5793(97)00958-7","article-title":"Proadrenomedullin N-terminal 20 peptide (PAMP) inhibits proliferation of human neuroblastoma TGW cells","volume":"413","author":"Ando","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0196-9781(99)00178-3","article-title":"Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin bind to teratocarcinoma cells","volume":"21","author":"Moody","year":"2000","journal-title":"Peptides"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Maibach, F., Sadozai, H., Seyed Jafari, S.M., Hunger, R.E., and Schenk, M. (2020). Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.02105"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1158\/2326-6066.CIR-15-0143","article-title":"Reflections on the Histopathology of Tumor-Infiltrating Lymphocytes in Melanoma and the Host Immune Response","volume":"3","author":"Mihm","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"106939","DOI":"10.1016\/j.intimp.2020.106939","article-title":"Effects of immune cells and cytokines on inflammation and immunosuppression in the tumor microenvironment","volume":"88","author":"Li","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_50","first-page":"761378","article-title":"Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous melanoma","volume":"2015","author":"Sotto","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/s41586-022-04682-5","article-title":"Landscape of helper and regulatory antitumour CD4+ T cells in melanoma","volume":"605","author":"Oliveira","year":"2022","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/bjc.2017.220","article-title":"HYPE or HOPE: The prognostic value of infiltrating immune cells in cancer","volume":"117","author":"Barnes","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2018.11.043","article-title":"Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma","volume":"176","author":"Li","year":"2019","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41571-019-0175-7","article-title":"Regulatory T cells in cancer immunosuppression\u2014Implications for anticancer therapy","volume":"16","author":"Togashi","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"104119","DOI":"10.1016\/j.cellimm.2020.104119","article-title":"The roles of tumor-associated macrophages in tumor angiogenesis and metastasis","volume":"353","author":"Fu","year":"2020","journal-title":"Cell Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jcpa.2014.07.003","article-title":"Immunohistochemical expression of ionized calcium binding adapter molecule 1 in cutaneous histiocytic proliferative, neoplastic and inflammatory disorders of dogs and cats","volume":"151","author":"Pierezan","year":"2014","journal-title":"J. Comp. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.7150\/thno.26888","article-title":"Arg1 expression defines immunosuppressive subsets of tumor-associated macrophages","volume":"8","author":"Arlauckas","year":"2018","journal-title":"Theranostics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1046\/j.1365-2567.2002.01452.x","article-title":"Insight into the potential for DNA idiotypic fusion vaccines designed for patients by analysing xenogeneic anti-idiotypic antibody responses","volume":"107","author":"Forconi","year":"2002","journal-title":"Immunology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6626","DOI":"10.4049\/jimmunol.177.10.6626","article-title":"Prime-boost with alternating DNA vaccines designed to engage different antigen presentation pathways generates high frequencies of peptide-specific CD8+ T cells","volume":"177","author":"Radcliffe","year":"2006","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12943-023-01885-w","article-title":"Exploiting innate immunity for cancer immunotherapy","volume":"22","author":"Yi","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jaci.2016.06.033","article-title":"Interleukins (from IL-1 to IL-38), interferons, transforming growth factor \u03b2, and TNF-\u03b1: Receptors, functions, and roles in diseases","volume":"138","author":"Akdis","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5490","DOI":"10.1073\/pnas.82.16.5490","article-title":"Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2)","volume":"82","author":"Hirano","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.4049\/jimmunol.128.6.2563","article-title":"Modulation of lymphocyte migration by human lymphokines. I. Identification and characterization of chemoattractant activity for lymphocytes from mitogen-stimulated mononuclear cells","volume":"128","author":"Center","year":"1982","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.4049\/jimmunol.182.2.1041","article-title":"Regulation of the foxp3 gene by the Th1 cytokines: The role of IL-27-induced STAT1","volume":"182","author":"Ouaked","year":"2009","journal-title":"J. Immunol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/6\/586\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:43:42Z","timestamp":1760031822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/6\/586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":64,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["vaccines13060586"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13060586","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]}}}