Differential regulation and function of tumor-infiltrating T cells in different stages of breast cancer patients

Breast cancer survival was associated with higher frequencies of CD8⁺ T cytotoxic T cells in infiltrating lymphocytes. On the other hand, the frequency of CD4⁺CD25⁺FoxP3⁺ regulatory T cells was inversely correlated with clinical outcomes of breast cancer. The regulation and interaction of different types of tumor-infiltrating T cells in different stages of breast cancer patients are still unclear. In this study, we examined the functions and regulations of CD8⁺ T cells and CD4⁺CD25⁺FoxP3⁺ T cells from resected tumors from 12 stage I, 24 stage II, and 20 stage III untreated breast cancer patients. We found that tumor-infiltrating CD8⁺ T cells from stage III patients were more refractory to T cell receptor (TCR) stimulation than those from stage I and stage II patients in terms of interferon gamma (IFN-γ) production and proliferation. On the other hand, tumor-infiltrating CD4⁺CD25⁺FoxP3⁺ T cells had higher proliferation in stage III tumors than in stage I and stage II tumors. In addition, we found that tumor-infiltrating CD4⁺CD25⁺ T cells can suppress CD8⁺ T cell inflammation ex vivo. Altogether, our data demonstrated that stage III tumors in breast cancer patients had a more immunosuppressive microenvironment.