Identification of naturally occurring tumor-reactive CD8+ T cells in human breast cancer patients
Colt Egelston, Diana Simons, Sailesh Gopalakrishna-Pillai, Grecia Jimenez, Christian Avalos, Peter P. Lee
Department of Immuno-Oncology, City of Hope National Medical Center, Duarte, CA
The presence of tumor infiltrating lymphocytes (TILs) in breast cancer patient tumors has been shown to correlate with patient outcome in certain molecular subtypes. However, while tumor-specific T cells have been identified in cancers such as melanoma and ovarian cancer, tumor-reactive CD8+ T cells in breast cancer patients have yet to be described. To examine human breast tumor TILs for the presence of tumor-reactive CD8+ T cells tumor tissue was surgically resected and immediately processed into single cell suspensions for immediate flow cytometry analysis. We found expression of the T cell activation marker CD137 on less than 5% of tumor infiltrating CD8+ T cells in 18/20 patients. Expression of activation markers OX-40 and HLA-DR was similarly minimal in patients surveyed. Furthermore, only 2/30 patients screened were found to contain tumor reactive CD8+ T cells when re-challenged with autologous tumor cells and measured for increased CD137 expression. Unique T cell clones generated from these patients were further shown to react against and to be able to kill various breast cancer cell lines, suggesting antigen specificity for shared self-antigens rather than mutated neo-antigens. Our findings suggest that while naturally occurring tumor reactive T cells may not be common in breast cancer patients, there is potential for such in a subset of patients. Approaches to either boost or induce tumor reactive T cells in breast cancer patients may be critical for successful immunotherapy-based treatments.