Abstract A23: Effects of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation and resistance to tumor relapse

Abstract

Abstract Both anti-CTLA-4 and anti-PD-1 mediate significant response rates in cancer patients. As a hallmark of successful immunotherapies, they also mediate durable responses that last for years. For example, anti-CTLA-4 mediates a 22% 10-year overall survival rate, while anti-PD-1 mediates a 34% 5-year overall survival rate. Because of the broader uses of immunotherapies, the number of patients who have tumor relapse also increases. About 25% of patients who initially responded to anti-PD-1 have tumor relapse within 24 months. However, the relationship between tumor relapse and long-term effect of immunotherapies is still not clear. The goal of this study is to understand the differential effect of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation in murine tumor models. By rechallenging mice with tumor cells that have had tumors previously eradicated by either treatment, our results have shown that anti-CTLA-4 induces a more durable memory antitumor response compared to that treated with anti-PD-1. By tracing the antigen-specific CD8 T-cells throughout the memory phase, anti-CTLA-4 increases the frequency and cytokine production of antigen-specific T cells compared with anti-PD-1. We have also found that anti-CTLA-4 induces the population of KLRG1+ effector CD8 T cells among the effectors compared with anti-PD-1 during rechallenge, despite the ratio between central memory and effectors remaining the same. Our studies enable us to identify the long-term effect of immunotherapies on immune system. Citation Format: Stephen Mok, Colm R. Duffy, Nana-Ama A. Anang, James P. Allison. Effects of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation and resistance to tumor relapse [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A23.