Background: Immune responses protect against tumors. Conventional chemotherapy may treat cancer but its efficacy is compromised by tumor relapse. Chemotherapy "per se" have immunostimulatory effects and sustain an antitumor T cell response. Anti-PD1 antibodies are used in clinics to boost immune responses blocking of an inhibitor receptor on T cells. We evaluated the T cell repertoire and cytokines in eight NSCLC patients who underwent anti-PD1 therapy after chemotherapy. Methods: We used PBMC to study T cell repertoire by "Spectratyping" a PCR based technique, and production of γ- IFN, IL-2, IL-4, IL-12, IL-13 and IL-17 by Quantitative PCR. Presence of cytokine message was then confirmed measuring the protein in the sera. Each patient was studied at the end of chemotherapy and after each anti-PD1 shot. Results: We found that chemotherapy shaped a specific T cell repertoire in these patients, expanding several T cell clonotypes that were maintained by anti-PD1 administration undergoing a long-lasting expansion. Of note, a prolonged effect in term of clinical outcome was paired by a consolidated production of IL-12 and γ-IFN. Conclusions: These data show that chemotherapy reshapes a T cell repertoire involved in antitumor response and the functional profile of these cells marked a prolonged efficient anti-tumor T cell response. Although preliminary, these results help to understand how monitor the patients undergoing therapy with anti immune-checkpoints. This is of critical importance due to the need to identify biomarkers and monitoring tools to optimize the use of these drugs, considering the high costs of these therapies.
Dept. of Clinical & Experimental Medicine, Second University of Naples