Firing up the cold tumors by targeting Vps34

Oncoimmunology. 2020 Aug 31;9(1):1809936. doi: 10.1080/2162402X.2020.1809936.

Abstract

Cancer immunotherapy based on anti-PD-1/PD-L1 blockade is particularly effective in responding to patients with hot tumors. These tumors are characterized by the accumulation of proinflammatory cytokines and T cell infiltration. In our recent report published in Science Advances, we demonstrate that targeting the autophagy-related protein Vps34 switched cold immune desert tumors into hot inflamed immune-infiltrated tumors and enhanced the efficacy of anti-PD-1/PD-L1. Our study provides the preclinical rationale to set up combination immunotherapy clinical trials using selective Vps34 inhibitors and immune checkpoint blockers in melanoma and CRC.

Keywords: Autophagy; CCL5; CXCL10; NK cells; T CD8 lymphocytes; VPS34; anti-PD-1/PD-L1; cancer immunotherapy; cold/hot tumors; colon cancer; immune landscape; melanoma; proinflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autophagy-Related Proteins
  • Humans
  • Immunologic Factors
  • Immunotherapy*
  • Melanoma* / drug therapy

Substances

  • Autophagy-Related Proteins
  • Immunologic Factors

Grants and funding

This work was supported by grants from Luxembourg National Research Fund C18/BM/12670304/COMBATIC; Roche pharma and Action LIONS Vaincre le Cancer Luxembourg; Fondation Cancer Luxembourg (FC/2018/06); Kriibskrank Kanner Foundation (2016-08-15); Janssen Cilag Pharma.