2. Academic Validation
  3. CD8 agonism functionally activates memory T cells and enhances antitumor immunity

CD8 agonism functionally activates memory T cells and enhances antitumor immunity

  • Int J Cancer. 2022 Sep 1;151(5):797-808. doi: 10.1002/ijc.34059.
Alaa Madi 1 2,  Nina Weisshaar 1,  Michael Buettner 3,  Gernot Poschet 3,  Sicong Ma 1,  Jingxia Wu 1,  Alessa Mieg 1 2,  Marvin Hering 1 2,  Yanan Ming 1,  Kerstin Mohr 1,  Nora Ten Bosch 1 4,  Guoliang Cui 1 2 4
Affiliations

Affiliations

  • 1 T Cell Metabolism Group (D192), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 2 Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
  • 3 Metabolomics Core Technology Platform, Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.
  • 4 Helmholtz Institute for Translational Oncology (HI-TRON), Mainz, Germany.
PMID: 35499751 DOI: 10.1002/ijc.34059
Abstract

Memory CD8+ T cells mature after antigen clearance and ultimately express CD8 protein at levels higher than those detected in effector CD8+ T cells. However, it is not clear whether engagement of CD8 in the absence of antigenic stimulation will result in the functional activation of T cells. Here, we found that CD8 antibody-mediated activation of memory CD8+ T cells triggered T cell receptor (TCR) downstream signaling, enhanced T cell-mediated cytotoxicity and promoted effector cytokine production in a glucose- and glutamine-dependent manner. Furthermore, pretreatment of memory CD8+ T cells with an agonistic anti-CD8 antibody enhanced their tumoricidal activity in vitro and in vivo. From these studies, we conclude that CD8 agonism activates glucose and glutamine metabolism in memory T cells and enhances the efficacy of memory T cell-based Cancer Immunotherapy.

Keywords

CD8+ T cells; TCR signaling; immunometabolism; immunotherapy; memory T cells.

Figures
Products