TCR use and cytokine response in PD-1 blockade.

3027 Background: PD-1 blockade releases effector T-cells in the tumor microenvironment, but little is known on the effects in peripheral blood. We used T cell receptor (TCR) sequencing and multiplex serum cytokine analysis to assess treatment-induced changes and correlation with clinical response. Methods: Patients with metastatic melanoma were administered PD-1 inhibitor pembrolizumab (MK-3475) across three clinical trials at UCLA (NCT01295827, NCT01704287, NCT01866319). Among those consenting to blood collection (UCLA IRB#10-000870), we selected cases with paired samples (baseline and at second dose), yielding 19 responders and 22 non-responders per irRECIST. Peripheral TCRs were sequenced by immunoSEQ assay (Adaptive Biotechnology). Serum cytokines were analyzed by Milliplex 38 Cytokine kit (HCYTMAG-60K-PX38). Mann-Whitney and Wilcox signed-rank tests evaluated group differences and treatment effects. Results: Unlike previous reports with CLTA4 blockade, anti-PD-1 treatment itself did not cause a net e...