Distribution of CD4+ and CD8+ exhausted tumor-infiltrating lymphocytes in molecular subtypes of Chinese breast cancer patients.

ABSTRACT

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.