Metabolic regulation of the mitochondrial immune checkpoint

Oncoimmunology. 2024 Aug 26;13(1):2394247. doi: 10.1080/2162402X.2024.2394247. eCollection 2024.

Abstract

Disrupting mitochondrial function in malignant cells is a promising strategy to enhance anticancer immunity. We have recently demonstrated that depriving colorectal cancer cells of serine results in mitochondrial dysfunction coupled with the cytosolic accumulation of mitochondrial DNA and consequent activation of CGAS- and STING-dependent tumor-targeting immune responses.

Keywords: Apoptotic caspases; BCL2; MOMP; immune checkpoint inhibition; senescence; type I interferon.

Publication types

  • Editorial

MeSH terms

  • Animals
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • DNA, Mitochondrial* / genetics
  • DNA, Mitochondrial* / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mitochondria* / metabolism
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / immunology
  • Nucleotidyltransferases / metabolism

Substances

  • cGAS protein, human
  • DNA, Mitochondrial
  • Membrane Proteins
  • Nucleotidyltransferases
  • STING1 protein, human

Grants and funding

DCM is supported by Institutional Research Grant 21-143-01-IRG from the American Cancer Society and startup funds from the Stony Brook Cancer Center and Bahl Center for Metabolomics and Imaging. The LG lab is/has been supported (as a PI unless otherwise indicated) by one NIH R01 grant (#CA271915), by two Breakthrough Level 2 grants from the US DoD BCRP (#BC180476P1, #BC210945), by a grant from the STARR Cancer Consortium (#I16-0064), by a Transformative Breast Cancer Consortium Grant from the US DoD BCRP (#W81XWH2120034, PI: Formenti), by a U54 grant from NIH/NCI (#CA274291, PI: Deasy, Formenti, Weichselbaum), by the 2019 Laura Ziskin Prize in Translational Research (#ZP-6177, PI: Formenti) from the Stand Up to Cancer (SU2C), by a Mantle Cell Lymphoma Research Initiative (MCL-RI, PI: Chen-Kiang) grant from the Leukemia and Lymphoma Society (LLS), by a Rapid Response Grant from the Functional Genomics Initiative (New York, US), by a pre-SPORE grant (PI: Demaria, Formenti), a Collaborative Research Initiative Grant and a Clinical Trials Innovation Grant from the Sandra and Edward Meyer Cancer Center (New York, US), by startup funds from the Dept. of Radiation Oncology at Weill Cornell Medicine (New York, US), by industrial collaborations with Lytix Biopharma (Oslo, Norway), Promontory (New York, US) and Onxeo (Paris, France), as well as by donations from Promontory (New York, US), the Luke Heller TECPR2 Foundation (Boston, US), Sotio a.s. (Prague, Czech Republic), Lytix Biopharma (Oslo, Norway), Onxeo (Paris, France), Ricerchiamo (Brescia, Italy), and Noxopharm (Chatswood, Australia).