{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:13:05Z","timestamp":1775146385442,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Mycosis fungoides (MF) is the predominant subtype of cutaneous T-cell lymphoma, whereas large plaque parapsoriasis (LPP) closely resembles early-stage MF, making differential diagnosis challenging. Immune markers, such as CD47, CD163, and B7-H3, play crucial roles in tumor immune evasion and macrophage polarization. However, their expression profiles and potential diagnostic or prognostic implications in early-stage MF and LPP remain poorly defined. Therefore, this study aimed to evaluate the expression of CD47, CD163, and B7-H3 in early-stage MF and LPP and analyze their associations with clinicopathological characteristics and patient outcomes. Materials and Methods: This retrospective study evaluated the immunohistochemical expression of CD47, CD163, and B7-H3 in 46 patients with early-stage mycosis fungoides (MF) and 46 patients with large plaque parapsoriasis (LPP). Expression levels were assessed using an immunoreactivity scoring system and analyzed for their associations with clinical parameters and disease-free survival (DFS). The study included patients diagnosed and followed at Sivas Cumhuriyet University between 1 March 2015 and 31 March 2025. Results: High CD47 expression was detected in 72.7% of MF patients, high B7-H3 expression in 45.7%, and high CD163 expression in 46.7% compared with LPP patients (p &lt; 0.001). These markers showed positive correlations, and elevated expression, especially of B7-H3 and CD163, was associated with shorter disease-free survival in univariate analysis. Conclusions: The higher expression of CD47, CD163, and B7-H3 in early-stage MF compared with LPP suggests that these markers may contribute to the differential diagnosis and could represent potential therapeutic targets; however, their independent prognostic value requires confirmation in larger studies.<\/jats:p>","DOI":"10.3390\/medicina62040678","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:14:43Z","timestamp":1775142883000},"page":"678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Immune Microenvironment in Early-Stage Mycosis Fungoides and Large-Plaque Parapsoriasis: Diagnostic and Prognostic Significance of CD47, CD163, and B7-H3"],"prefix":"10.3390","volume":"62","author":[{"given":"Rukiye","family":"Yasak Guner","sequence":"first","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9418-8862","authenticated-orcid":false,"given":"Ramazan Oguz","family":"Y\u00fcceer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet Turan","family":"Unsal","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1111\/ijd.16098","article-title":"Mycosis fungoides in pediatric population: Comprehensive review on epidemiology, clinical presentation, and management","volume":"61","author":"Kothari","year":"2022","journal-title":"Int. J. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.clindermatol.2019.01.004","article-title":"Mycosis fungoides: A great imitator","volume":"37","author":"Hodak","year":"2019","journal-title":"Clin. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s13555-022-00716-y","article-title":"Parapsoriasis\u2014A diagnosis with an identity crisis: A narrative review","volume":"12","author":"Chairatchaneeboon","year":"2022","journal-title":"Dermatol. Ther."},{"key":"ref_4","first-page":"e57545","article-title":"Decoding early mycosis fungoides: Histopathologic and immunohistochemical clues","volume":"16","author":"Terzi","year":"2024","journal-title":"Cureus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1111\/bjd.14605","article-title":"Systematic review of cases of cutaneous T-cell lymphoma transformation in pityriasis lichenoides and small plaque parapsoriasis","volume":"175","author":"Sibbald","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3892\/ol.2024.14389","article-title":"Progress in cancer research on the regulator of phagocytosis CD47, which determines the fate of tumor cells (Review)","volume":"27","author":"Wu","year":"2024","journal-title":"Oncol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.1073\/pnas.1121623109","article-title":"The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors","volume":"109","author":"Willingham","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","first-page":"4465","article-title":"Prognostic significance of CD68, CD163 and folate receptor-\u03b2 positive macrophages in hepatocellular carcinoma","volume":"15","author":"Minami","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Basak, U., Sarkar, T., Mukherjee, S., Chakraborty, S., Dutta, A., Dutta, S., Nayak, D., Kaushik, S., Das, T., and Sa, G. (2023). Tumor-associated macrophages: An effective player of the tumor microenvironment. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1295257"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1158\/1538-7445.AM2025-4875","article-title":"B7-H3 (CD276) regulates the migration and infiltration of tumor-associated macrophages","volume":"85","author":"Kang","year":"2025","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12943-023-01751-9","article-title":"New frontiers in immune checkpoint B7-H3 (CD276) research and drug development","volume":"22","author":"Getu","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zi, Z., Zhao, H., Wang, H., Ma, X., and Wei, F. (2020). B7-H3 chimeric antigen receptor redirected T cells target anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. Cancers, 12.","DOI":"10.3390\/cancers12123815"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.jaad.2005.08.057","article-title":"Defining early mycosis fungoides","volume":"53","author":"Pimpinelli","year":"2005","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yang, J., Tian, Z., Gao, H., Xiong, F., Cao, C., Yu, J., Shi, W., Zhan, Q., and Yang, C. (2022). Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09639-5"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/labinvest.2016.70","article-title":"Relationship between tumor-associated macrophage subsets and CD47 expression in squamous cell carcinoma of the head and neck in the tumor microenvironment","volume":"96","author":"Sakakura","year":"2016","journal-title":"Lab. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kwantwi, L.B., Rosen, S.T., and Querfeld, C. (2024). The Tumor Microenvironment as a Therapeutic Target in Cutaneous T-Cell Lymphoma. Cancers, 16.","DOI":"10.3390\/cancers16193368"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/cup.14155","article-title":"Potential role of tumor-associated macrophages and CD163\/CD68 ratio in mycosis fungoides and S\u00e9zary syndrome in correlation with serum sCD163 and CCL22","volume":"49","author":"Elgarhy","year":"2022","journal-title":"J. Cutan. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.21608\/amj.2020.120657","article-title":"Study of the role of serum CD163 as a prognostic tool in mycosis fungoides therapy","volume":"49","author":"Mohammed","year":"2020","journal-title":"Al-Azhar Med. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00011-024-01907-3","article-title":"Dissection of pro-tumoral macrophage subtypes and immunosuppressive cells participating in M2 polarization","volume":"73","author":"Sezginer","year":"2024","journal-title":"Inflamm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jdermsci.2012.07.007","article-title":"Association of the numbers of CD163(+) cells in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma","volume":"68","author":"Sugaya","year":"2012","journal-title":"J. Dermatol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1200\/JCO.2014.60.3969","article-title":"Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and S\u00e9zary syndrome with variable CD30 expression level: A multi-institution collaborative project","volume":"33","author":"Kim","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Xiao, A., and Akilov, O.E. (2022). Targeting the CD47-SIRP\u03b1 axis: Present therapies and the future for cutaneous T-cell lymphoma. Cells, 11.","DOI":"10.3390\/cells11223591"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jiang, T.T., Kruglov, O., Lin, G.H.Y., Minic, A., Jordan, K., Uger, R.A., Wong, M., Shou, Y., and Akilov, O.E. (2021). Clinical response to anti-CD47 immunotherapy is associated with rapid reduction of exhausted bystander CD4+ BTLA+ T cells in tumor microenvironment of mycosis fungoides. Cancers, 13.","DOI":"10.3390\/cancers13235982"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1158\/1078-0432.CCR-15-2428","article-title":"Molecular pathways: Targeting B7-H3 (CD276) for human cancer immunotherapy","volume":"22","author":"Picarda","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6","DOI":"10.21320\/2500-2139-2016-9-1-6-12","article-title":"Prognostic significance of thymidine kinase-1 versus \u03b22-microglobulin and lactate dehydrogenase in lymphoproliferative diseases","volume":"9","author":"Parilova","year":"2016","journal-title":"Clin. Oncohematol."},{"key":"ref_27","first-page":"6519","article-title":"High expression of B7-H3 and CD163 in cancer tissues indicates malignant clinicopathological status and poor prognosis of patients with urothelial cell carcinoma of the bladder","volume":"15","author":"Xu","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s12105-020-01222-3","article-title":"Evaluation Challenges in the Validation of B7-H3 as Oral Tongue Cancer Prognosticator","volume":"15","author":"Wirsing","year":"2021","journal-title":"Head Neck Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.oraloncology.2019.04.019","article-title":"Prognostic significance of CD68+ and CD163+ tumor associated macrophages in head and neck squamous cell carcinoma: A systematic review and meta-analysis","volume":"93","author":"Troiano","year":"2019","journal-title":"Oral Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13000-023-01320-0","article-title":"B7-H3 expression is associated with high PD-L1 expression in clear cell renal cell carcinoma and predicts poor prognosis","volume":"18","author":"Lee","year":"2023","journal-title":"Diagn. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Y\u00fcceer, R.O., Kaya, S., Balc\u0131, S.N., E\u011filmez, H.R., Y\u0131lmaz, M., and Erd\u0131s, E. (2025). Prognostic Biomarkers in Isocitrate Dehydrogenase Wild-Type Glioblastoma: A Focus on B7-H3. Brain Sci., 15.","DOI":"10.3390\/brainsci15020212"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/678\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:42:36Z","timestamp":1775144556000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["medicina62040678"],"URL":"https:\/\/doi.org\/10.3390\/medicina62040678","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]}}}