37P Lymphocyte subpopulation balances as a blood biomarker for immune-related adverse events in patients receiving immune checkpoint inhibitors

immunologic analyses were performed using IFN-g ELISpot, flow cytometry on PBMC and Bulk RNA sequencing on circulating sorted CD4 T cells.Results: A high frequency of circulating tumor-specific CD4 Th1 response, i.e response against at least one of the 3 antigens tested (hTERT, MAGE-A3 and KK-LC1), was found in all 3 groups (76%, 63%, 68% in CD, R1, R2, respectively).Among the 3 antigens tested, the circulating hTERT-specific CD4 Th1 response frequency was higher in CD compared to R1 and R2 : 70% vs 25% vs 40% positive response (**, p<0.01).Furthermore, CD4 Th1 polyspecific responses, i.e against at least 2 of the 3 antigens tested were more detected in CD pts (31 pts, 62%) compared to 15 (42%) and 7 (32%) pts in R2 and R1 respectively.hTERT-specific CD4 Th1 exhibits cytotoxic phenotype and a modified memory profile compared to non-specific CD4 T cells.Transcriptomic analyses of CD4 T cells revealed 669 genes upregulated and 52 down-regulated in CD pts, mainly enriched in Th1-associated pathways such as IFN-g response, TNF-a signaling via NF-kB and IL-2-STAT5 signaling compared to healthy donors.Analyses of immune-related genes showed upregulation of cytotoxic markers in CD pts compared to R1 and R2. Conclusions:In conclusion, our data demonstrated that cytotoxic hTERT-specific CD4 Th1 response is involved in the long-term response to ICI.