Background Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear.
Methods We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed.
Results Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort.
Conclusions Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.
Citations
Citations to this article as recorded by
Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy Chiara Corti, Busem Binboğa Kurt, Beyza Koca, Tasnim Rahman, Fabio Conforti, Laura Pala, Giampaolo Bianchini, Carmen Criscitiello, Giuseppe Curigliano, Ana C. Garrido-Castro, Sheheryar K. Kabraji, Adrienne G. Waks, Elizabeth A. Mittendorf, Sara M. Tolaney Cancer Treatment Reviews.2025; 132: 102852. CrossRef
MHC-I upregulation by macbecin II in the solid tumors potentiates the effect of active immunotherapy Ravindra Pramod Deshpande, Kerui Wu, Shih-Ying Wu, Abhishek Tyagi, Eleanor C Smith, Jee-Won Kim, Kounosuke Watabe EMBO Molecular Medicine.2025;[Epub] CrossRef
Programmed Cell Death Ligand 1 (PD-L1) and major Histocompatibility Complex Class I (MHC Class I) Expression Patterns and Their Pathologic Associations in triple-Negative Breast Cancer Ponkrit Kaewkedsri, Piyapharom Intarawichian, Sirawich Jessadapattarakul, Waritta Kunprom, Supinda Koonmee, Malinee Thanee, Ongart Somintara, Anongporn Wongbuddha, Payia Chadbunchachai, Supajit Nawapun, Chaiwat Aphivatanasiri Breast Cancer: Targets and Therapy.2025; Volume 17: 123. CrossRef
Comment on “Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta‑Analysis” Wei Han, Li-zhou Shi, Yu-wei Zhang, Hao-nan Wang Molecular Diagnosis & Therapy.2024; 28(2): 237. CrossRef
Immunotherapy resistance in solid tumors: mechanisms and potential solutions Daniel S. Lefler, Steven A. Manobianco, Babar Bashir Cancer Biology & Therapy.2024;[Epub] CrossRef
Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications Terufumi Kubo, Shiori Asano, Kenta Sasaki, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe HLA.2024;[Epub] CrossRef
Human Leukocyte Antigen Class I Expression and Natural Killer Cell Infiltration and Its Correlation with Prognostic Features in Luminal Breast Cancers Maria Vernet-Tomas, Ivonne Vazquez, Francesc Olivares, David Lopez, Jose Yelamos, Laura Comerma Breast Cancer: Targets and Therapy.2024; Volume 16: 657. CrossRef
Upregulation of MHC I antigen processing machinery gene expression in breast cancer cells by Trichostatin A A. H. Murtadha, N. A. Sharudin, I. I.M. Azahar, A. T. Che Has, N. F. Mokhtar Молекулярная биология.2024; 58(1): 121. CrossRef
HLA-I and breast cancer prognosis: A systematic review and meta-analysis Francisco Cezar Aquino de Moraes, Jorge Henrique Cavalcanti Orestes Cardoso, Francinny Alves Kelly, Michele Kreuz, Lilianne Rodrigues Fernandes, Maria Cristina Figueroa Magalhães, Rommel Mario Rodríguez Burbano Human Immunology.2024; 85(6): 111148. CrossRef
Cancer Immunology: Immune Escape of Tumors—Expression and Regulation of HLA Class I Molecules and Its Role in Immunotherapies Yuan Wang, Simon Jasinski-Bergner, Claudia Wickenhauser, Barbara Seliger Advances in Anatomic Pathology.2023; 30(3): 148. CrossRef
In Silico Pipeline to Identify Tumor-Specific Antigens for Cancer Immunotherapy Using Exome Sequencing Data Diego Morazán-Fernández, Javier Mora, Jose Arturo Molina-Mora Phenomics.2023; 3(2): 130. CrossRef
HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events Ning Jiang, Yue Yu, Dawei Wu, Shuhang Wang, Yuan Fang, Huilei Miao, Peiwen Ma, Huiyao Huang, Min Zhang, Yu Zhang, Yu Tang, Ning Li Journal of Cancer Research and Clinical Oncology.2023; 149(2): 737. CrossRef
Relationship between Systemic Inflammatory Markers, GLUT1 Expression, and Maximum 18F-Fluorodeoxyglucose Uptake in Non-Small Cell Lung Carcinoma and Their Prognostic Significance Sonya Youngju Park, Deog-Gon Cho, Byoung-Yong Shim, Uiju Cho Diagnostics.2023; 13(6): 1013. CrossRef
Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis Weiqiang Qiao, Zhiqiang Jia, Wanying Guo, Qipeng Liu, Xiao Guo, Miao Deng Molecular Diagnosis & Therapy.2023; 27(5): 573. CrossRef
Challenges and solutions for therapeuticTCR‐based agents Manish Malviya, Zita E. H. Aretz, Zaki Molvi, Jayop Lee, Stephanie Pierre, Patrick Wallisch, Tao Dao, David A. Scheinberg Immunological Reviews.2023; 320(1): 58. CrossRef
Molecular mechanisms of impaired antigenic presentation as a cause of tumor escape from immune surveillance A.A. Korotaeva, A.A. Borunova, A.Yu. Kuzevanova, T.N. Zabotina, A.A. Alimov Arkhiv patologii.2023; 85(6): 76. CrossRef
Immune Escape Mechanism of Cancer Ayse Caner Current Molecular Biology Reports.2023; 10(1): 9. CrossRef
Upregulation of MHC I Antigen Processing Machinery Gene Expression in Breast Cancer Cells by Trichostatin A A. H. Murtadha, N. A. Sharudin, I. I. M. Azahar, A. T. Che Has, N. F. Mokhtar Molecular Biology.2023; 57(6): 1212. CrossRef
Human Leukocyte Antigen Class I Antigen-Processing Machinery Upregulation by Anticancer Therapies in the Era of Checkpoint Inhibitors Ananthan Sadagopan, Theodoros Michelakos, Gabriella Boyiadzis, Cristina Ferrone, Soldano Ferrone JAMA Oncology.2022; 8(3): 462. CrossRef
Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response Brandie C. Taylor, Justin M. Balko Frontiers in Immunology.2022;[Epub] CrossRef
Immune Checkpoint Blockade in Hormone Receptor-Positive Breast Cancer: Resistance Mechanisms and Future Perspectives Ioannis A. Vathiotis, Ioannis Trontzas, Niki Gavrielatou, Georgia Gomatou, Nikolaos K. Syrigos, Elias A. Kotteas Clinical Breast Cancer.2022; 22(7): 642. CrossRef
Aberrant synaptophysin expression in classic Hodgkin lymphoma Soyoung Im, Jeong-A. Kim, Gyeongsin Park, Uiju Cho Diagnostic Pathology.2022;[Epub] CrossRef
Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer Song-Hee Han, Milim Kim, Yul Ri Chung, Ji Won Woo, Hye Yeon Choi, So Yeon Park Scientific Reports.2022;[Epub] CrossRef
Immune landscape and therapeutic strategies: new insights into PD-L1 in tumors Yuan Wei, Xiao Xiao, Xiang-Ming Lao, Limin Zheng, Dong-Ming Kuang Cellular and Molecular Life Sciences.2021; 78(3): 867. CrossRef
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer Leisha A Emens, Sylvia Adams, Ashley Cimino-Mathews, Mary L Disis, Margaret E Gatti-Mays, Alice Y Ho, Kevin Kalinsky, Heather L McArthur, Elizabeth A Mittendorf, Rita Nanda, David B Page, Hope S Rugo, Krista M Rubin, Hatem Soliman, Patricia A Spears, Sara Journal for ImmunoTherapy of Cancer.2021; 9(8): e002597. CrossRef
Resistance mechanisms to checkpoint inhibitors Sarah A Weiss, Mario Sznol Current Opinion in Immunology.2021; 69: 47. CrossRef
The Immunology of Hormone Receptor Positive Breast Cancer Jonathan Goldberg, Ricardo G. Pastorello, Tuulia Vallius, Janae Davis, Yvonne Xiaoyong Cui, Judith Agudo, Adrienne G. Waks, Tanya Keenan, Sandra S. McAllister, Sara M. Tolaney, Elizabeth A. Mittendorf, Jennifer L. Guerriero Frontiers in Immunology.2021;[Epub] CrossRef
B4GALNT2 Gene Promotes Proliferation, and Invasiveness and Migration Abilities of Model Triple Negative Breast Cancer (TNBC) Cells by Interacting With HLA-B Protein Pu Yu, Lili Zhu, Kang Cui, Yabing Du, Chaojie Zhang, Wang Ma, Jia Guo Frontiers in Oncology.2021;[Epub] CrossRef
Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies Nina Radosevic-Robin, Pier Selenica, Yingjie Zhu, Helen H. Won, Michael F. Berger, Lorenzo Ferrando, Emiliano Cocco, Maud Privat, Flora Ponelle-Chachuat, Catherine Abrial, Jean-Marc Nabholtz, Frederique Penault-Llorca, Jorge S. Reis-Filho, Maurizio Scaltr npj Breast Cancer.2021;[Epub] CrossRef
Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation? Liam Masterson, James Howard, Jazmina Gonzalez‐Cruz, Christopher Jackson, Catherine Barnett, Lewis Overton, Howard Liu, Rahul Ladwa, Fiona Simpson, Margie McGrath, Ben Wallwork, Terry Jones, Christian Ottensmeier, Melvin L.K. Chua, Chris Perry, Rajiv Khan International Journal of Cancer.2020; 146(8): 2305. CrossRef
Co-expression of HLA-I loci improved prognostication in HER2+ breast cancers Julia Y. Tsang, Chun-Sing Ho, Yun-Bi Ni, Yan Shao, Ivan K. Poon, Siu-Ki Chan, Sai-Yin Cheung, Ka-Ho Shea, Monalyn Marabi, Gary M. Tse Cancer Immunology, Immunotherapy.2020; 69(5): 799. CrossRef
Breast cancer patients overall survival depends on a combination of the polymorphisms of tumor necrosis factor gene and HLA-haplotypes T.F. Malivanova, E.V. Alferova, A.S. Ostashkin, T.A. Astrelina, N.N. Mazurenko Molecular Genetics Microbiology and Virology (Russian version).2020; 38(1): 40. CrossRef
The Overall Survival of Breast Cancer Patients Depends on a Combination of Polymorphisms of Tumor Necrosis Factor Gene and HLA Haplotypes T. F. Malivanova, E. V. Alferova, A. S. Ostashkin, T. A. Astrelina, N. N. Mazurenko Molecular Genetics, Microbiology and Virology.2020; 35(1): 38. CrossRef
The Emergence of Natural Killer Cells as a Major Target in Cancer Immunotherapy Fernando Souza-Fonseca-Guimaraes, Joseph Cursons, Nicholas D. Huntington Trends in Immunology.2019; 40(2): 142. CrossRef
We present a case of 55-year-old man who complained of dyspnea and sputum for a month. He was an ex-smoker with a history of prostate cancer and pulmonary tuberculosis. Chest radiographs revealed bilateral pleural effusions of a small to moderate amount. Pigtail catheters were inserted for drainage. The pleural fluid consisted of large clusters and tightly cohesive groups of malignant cells, which however could not be ascribed to prostate cancer with certainty. We performed immunocytochemical panel studies to determine the origin of cancer metastasis. The immunostaining results were positive for prostate-specific antigen, alpha-methylacyl-coenzyme A racemase, and Nkx 3.1, consistent with prostate cancer. Pleural effusion associated with prostate cancer is rare. To our knowledge, this is the first case report in Korea to describe cytologic features of malignant pleural effusion associated with prostate cancer.
Citations
Citations to this article as recorded by
Pleural Metastasis as an Initial Presentation of Prostate Cancer: Case Report and Literature Review Katarzyna Skrobisz, Kevin Miszewski, Laura Miszewska, Michał Bieńkowski, Marcin Matuszewski, Michał Studniarek Diagnostics.2025; 15(6): 666. CrossRef
EBUS-TBNA pleural biopsy reveals prostate cancer metastasis: A rare case report and review of the literature Fotios Sampsonas, Dimitrios Komninos, Vasilina Sotiropoulou, Matthaios Katsaras, Dimitra Gkanetsou, Ourania Papaioannou, Panagiota Tsiri, Vasiliki Tzelepi, Argyrios Tzouvelekis Pneumon.2024; 37(2): 1. CrossRef
Cytopathological Features of Extensive Bilateral Pleural Effusions in Metastatic Prostate Cancer: Report of a Rare Case Hehua Huang, Caroline Yap Cureus.2024;[Epub] CrossRef
Bilateral pleural effusion: etiology, diagnostics N. A. Stogova PULMONOLOGIYA.2022; 32(6): 885. CrossRef
Rare Metastatic Prostate Cancer Mimicking Lymphoma with Malignant Pleural Effusion Tung Liu, En Meng, Yu-Chun Lin, Tai-Kuang Chao, Yi-Ming Chang Journal of Medical Sciences.2021; 42(1): 46. CrossRef