Keynote Presentation: Discovery of novel targetable pathways to overcome immunotherapy resistance

The success of PD-1 blockade is predicated on the fact that a critical end-effector of anti-tumor immunity is the T cell. We and others have demonstrated the role of CD4+ (helper) and CD8+ (effector) T cells targeting epitopes derived from tumor somatic mutations (neoantigens) in response to anti-PD-1. Additionally, many groups have examined intratumoral characteristics of T cells at the single cell level in human cancers, but these studies suffer from a fundamental limitation: they cannot distinguish true tumor-specific T cells from T cells with irrelevant antigen specificity. In this presentation, I will demonstrate how our lab is developing innovative methods to better detect and study tumor-reactive TIL in the context of resectable lung cancers, and how we have discovered clinically meaningful interactions between tumor-reactive effector T cells and highly suppressive Treg in human tumors treated with neoadjuvant PD-1 blockade. 

Learning Objectives:

1. Understand the heterogeneity of tumor infiltrating Treg as a function of immunotherapy response

2. Discuss therapeutically relevant biology that we are able to discover by querying Treg at single cell resolution

3. Demonstrate how we can apply a mix of ex vivo, in vitro, in vivo, and in silico approaches to discover new therapeutic targets