4.7 Article

Firing up the cold tumors by targeting Vps34

Journal

ONCOIMMUNOLOGY
Volume 9, Issue 1, Pages -

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2020.1809936

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

Funding

  1. Luxembourg National Research Fund [C18/BM/12670304/COMBATIC]
  2. Action LIONS Vaincre le Cancer Luxembourg
  3. Fondation Cancer Luxembourg [FC/2018/06]
  4. Kriibskrank Kanner Foundation [2016-08-15]
  5. Janssen Cilag Pharma
  6. Roche pharma

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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 inScience 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.

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