Distribution of CD4+ and CD8+ exhausted tumor-infiltrating lymphocytes in molecular subtypes of Chinese breast cancer patients
Received 13 March 2018
Accepted for publication 12 August 2018
Published 21 September 2018 Volume 2018:11 Pages 6139—6145
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Feng Shi,1 Hong Chang,1 Quan Zhou,1 Yan-Jie Zhao,2 Guang-Jiang Wu,3 Qing-Kun Song4,5
1Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 2Department of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 3Department of Infection Control, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 4Department of Science and Technology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 5Department of Cancer Epidemiology, Beijing Key Laboratory of Cancer Therapeutic Vaccine, Beijing 100038, People’s Republic of China
Purpose: Breast cancer (BC) is the leading cancer affecting Chinese women; however, the immune microenvironment between molecular subtypes is less reported. This study aimed to investigate the distribution of tumor-infiltrating lymphocyte (TIL) subpopulations, especially exhausted CD4+ and CD8+ TILs in Chinese BC patients.
Patients and methods: A total of 133 patients with breast invasive ductal carcinoma were recruited consecutively from January 1, 2012 to December 31, 2013, and TILs were detected in H&E-stained sections. Expression profiling of PD-1, CD4, and CD8 was determined by immunohistochemistry on 4 µm formalin-fixed paraffin-embedded tissue sections. The distribution of TILs was analyzed based on hormone receptor status and molecular subtypes.
Results: PD-1+, CD4+, and CD8+ TILs distributed differently based on molecular subtypes. Compared to Luminal A, triple-negative breast cancer (TNBC) patients had more PD-1+ TILs (39/high-power field [HPF] vs 11/HPF), PD-1+ helper T (CD4+) cells (28/HPF vs 10/HPF), and PD-1+ cytotoxic (CD8+) T-cells (3/HPF vs 2/HPF).
Conclusion: TILs are distributed differently based on molecular subtypes. TNBC patients exhibit more PD-1+ exhausted TILs, representing an inhibitory immune microenvironment. PD-1/PD-L1 pathway is a potential therapeutic target of TNBC.
Keywords: breast cancer, tumor-infiltrating lymphocyte, PD-1, molecular subtype
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