RNA Polymerase Pausing Complex Promotes CD8+ T Cell Response in the Tumor Microenvironment 9355

Abstract Description Tumor immunity is influenced by CD8+ T cell responses, which have significant implications for hospitalization, treatment costs, and patient outcomes. However, the molecular mechanisms that control CD8+ T cell activity in the tumor microenvironment (TME) are not entirely known. The Negative Elongation Factor (NELF) complex, particularly the Nelfb subunit, plays a pivotal role in RNA polymerase II pausing and transcriptional regulation. Using a T cell-specific Nelfb conditional knockout model, this study targets to investigate the role of the Nelfb in CD8+ T cell response within the TME. Specifically, we evaluated (1) the impact of Nelfb on CD8+ T cell activation, proliferation, and effector functions in vitro; (2) the effect of Nelfb on tumor growth and progression in vivo using murine tumor models; and (3) the effect of Nelfb on CD8+ T cell infiltration, persistence, and exhaustion in the TME. Preliminary data suggests that Nelfb-deficient tumor-specific CD8+ T cells exhibit severe defects to accumulate inside the TME but not in the tumor-draining lymph nodes. In vivo studies reveal that Nelfb-deficient CD8+ T cells infiltrate tumors, however, fail to persist in the TME, data suggest Nelfb is critical for sustained anti-tumor immunity. The purpose of the research effort is to improve our understanding of transcriptional regulation in CD8+ T cell responses and to discover possible targets for therapeutic targets to boost anti-tumor immune responses. Funding Sources NIH grant R01CA288321 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)