Immunotherapy has revolutionized cancer treatment, but the benefits of immunotherapy are not ubiquitous or absolute. In breast cancer, higher levels of lymphocytic infiltrate confer significant prognostic advantage, predict response to chemotherapy in early stage disease and are associated with benefit from PD-1 inhibition. To enhance the modest benefits of immunotherapy seen in breast cancer thus far, it is expected that a greater understanding of the immune subpopulations in the tumor microenvironment will be necessary, emphasizing that the quality and quantity of tumor infiltrating lymphocytes are important. We have profiled the T cell infiltrate in primary and metastatic breast cancers, using flow cytometry, single cell mRNASeq, multiplex immunohistochemistry and bulk RNASeq on flow sorted CD8 populations. In this work, we found that CD8 T cells display tissue resident specialization. In particular, we confirmed the presence of a CD8 T cell population with tissue resident memory features. This population was notable for high expression of T cell checkpoint receptors and cytotoxic markers, active proliferation, and a distinct T cell receptor repertoire in contrast to CD8 effector memory T cells. A gene signature derived from this population was found to be prognostic in early stage breast cancer, and associated with benefit from PD-1 checkpoint inhibition in melanoma.
We find that single cell profiling in human samples is a powerful technique which unveils tissue resident aspects of the anti-cancer immune response. This approach may lead to better immune biomarkers and optimization of immunotherapeutic strategies.