Firing up the cold tumors by targeting Vps34

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
• vps34
• cold/hot tumors
• proinflammatory cytokines
• ccl5
• cxcl10
• immune landscape
• nk cells
• t cd8 lymphocytes
• cancer immunotherapy
• anti-pd-1/pd-l1
• melanoma
• colon cancer