CD8+ tissue resident memory T cells are associated with good prognosis in breast cancer patients

CD8+ Tumor Infiltrating Lymphocytes (TILs) have been shown to correlate with patient prognosis in breast cancer. Recently, resident memory T cells (TRM) have been established as a potent functional subset of memory T cells that exist in peripheral tissue without recirculation. We assayed CD8+ T cells from fresh breast tumors to phenotype memory T cells and found them to be almost exclusively made up of effector memory T cells. Further profiling by examining expression of CD103 and CD69 showed that on average 40% of CD8+ TILs are composed of TRM. Functional analysis of these T cells showed robust production of IFNγ and TNFα by these TRMs suggesting that despite existence in the tumor microenvironment TRMs maintain functional potency. To examine if CD8+ TRM have prognostic value in breast cancer patients, we examined a set of primary tumors from ‘good’ and ‘bad’ outcome patients, which we defined as having a relapse in more than 5 years after diagnosis or in less than 3 years after diagnosis respectively. In good outcome patients TRMs represented 60% of CD8+ T cells found in cancer islands, while only 20% of such in bad outcome patients. Similarly, CD8+ TRMs were observed in higher numbers in both the cancer islands and stroma of good outcome patient tumors in comparison to bad outcome patient tumors. This observed significance was greater than that found for CD8+ T cells in general, highlighting the importance of TRM in affecting patient outcome. Finally we showed that TRMs also exist in non-cancerous breast tissue and are found within the mammary ducts associated with epithelial cells perhaps in surveillance of potential pathogens. We suggest that TRMs are a potential vaccine target for preventing recurrence and metastasis in cancer patients.