Abstract 1366: A novel stem cell memory T cell subpopulation intermediate to canonical stem cell memory and central memory T cells in human cancer

Abstract

Abstract Stem memory T cells (Tscm) are integral for effective immunotherapy and antitumor responses, but little is known about Tscm immunobiology in solid human tumors. Here we identify self-renewing and multipotent Tscm tumor-infiltrating lymphocytes (TILs) in human cancer and present a novel Tscm subset which expresses CD45RO, is derived from CD45RO- Tscm T cells, and is capable of self-renewal and multipotency. From the analysis of CD45RO+ Tscm differentiation, phenotyping, gene expression, and the broader TCR repertoire, we find that CD45RO+ Tscm cells are hierarchically positioned in between canonical CD45RO- Tscm cells and central memory T cells. Notably, CD45RO+ Tscm cells exhibit a gene expression profile consistent with effector capabilities and a tumor-specific phenotype that is more similar to T cells associated with successful immunotherapy than canonical Tscm. Thus, we describe a novel Tscm subset in human cancer which has distinct phenotypic, transcriptional, and effector-like attributes that position it as an attractive subset for future basic and clinical research in the setting of cancer immunotherapy. Citation Format: Daniel J. Powell. A novel stem cell memory T cell subpopulation intermediate to canonical stem cell memory and central memory T cells in human cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1366.