Circulating Exhausted PD-1+CD39+ Helper CD4 T Cells Are Tumor-Antigen-Specific and Predict Response to PD-1/PD-L1 Axis Blockade
Résumé
Not all cancer patients receiving immunotherapy by immune checkpoint blockade experience a clinical benefit. Our study was aimed at identifying biomarkers that could guide the selection of immunotherapy-responsive patients. Immunotherapy targets two major populations of lymphocytes: CD8 T cells, which directly kill tumor cells, and CD4 T cells, which provide help to CD8 T cells, the role of which in clinical responsiveness to immunotherapy has been less explored. We identified, in the blood of cancer patients, a population of CD4 T cells expressing inhibitory receptors targeted by immunotherapy. We showed that these cells were activated and proliferating, indicating their potential involvement in ongoing immune responses. Accordingly, we showed that they were specific for tumor antigens. In a prospective cohort, we showed that high proportions of these cells prior to therapy were associated with a response to immunotherapy.
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