CD8+T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor

• Type of Material: Article
• Authors: Nataliya Prokhnevska, Emory University; Maria A Cardenas, Emory University; Rajesh M Valanparambil, Emory University; Ewelina Sobierajska, Emory University; Benjamin Barwick, Emory University; Caroline Jansen, Emory University; Adriana Reyes Moon, Emory University; Petra Gregorova, Emory University; Luke delBalzo, Emory University; Rachel Greenwald, Emory University; Mehmet Bilen, Emory University; Mehrdad Alemozaffar, Emory University; Shreyas Joshi, Emory University; Cara Cimmino, Emory University; Christian Larsen, Emory University; Viraj Master, Emory University; Martin Sanda, Emory University; Haydn Kissick, Emory University
• Language: English
• Date: 2023-01-10
• Publisher: CELL PRESS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.immuni.2022.12.002
• Title of Journal or Parent Work: IMMUNITY
• Volume: 56
• Issue: 1
• Start Page: 107
• End Page: +
• Keywords: CD8(+) T-CELLS; CLONAL EXPANSION; DENDRITIC CELLS; PD-1 BLOCKADE; ANTIGEN; NAIVE; 3RD SIGNAL; Life Sciences & Biomedicine; Science & Technology; Immunology; EXHAUSTION; PROVIDE; IMMUNOTHERAPY

Abstract

Improvements in tumor immunotherapies depend on better understanding of the anti-tumor T cell response. By studying human tumor-draining lymph nodes (TDLNs), we found that activated CD8+ T cells in TDLNs shared functional, transcriptional, and epigenetic traits with TCF1+ stem-like cells in the tumor. The phenotype and TCR overlap suggested that these TDLN cells were precursors to tumor-resident stem-like CD8+ T cells. Murine tumor models revealed that tumor-specific CD8+ T cells were activated in TDLNs but lacked an effector phenotype. These stem-like cells migrated into the tumor, where additional co-stimulation from antigen-presenting cells drove effector differentiation. This model of CD8+ T cell activation in response to cancer is different from that of canonical CD8+ T cell activation to acute viruses, and it proposes two stages of tumor-specific CD8+ T cell activation: initial activation in TDLNs and subsequent effector program acquisition within the tumor after additional co-stimulation.