Targeting autophagy blocks melanoma growth by bringing natural killer cells to the tumor battlefield

Muhammad Zaeem Noman, Guy Berchem, Bassam Janji*

*Corresponding author for this work

Research output: Contribution to journalComment/debate

22 Citations (Scopus)

Abstract

Solid tumors are able to establish and sustain an immune suppressive microenvironment, which prevents the infiltration of cytotoxic effector immune cells into the tumor bed. We showed that genetic targeting of the macroautophagy/autophagy gene Becn1/Beclin1 in B16-F10 tumors inhibits their growth by inducing a massive infiltration of functional natural killer (NK) cells into the tumor bed. Such infiltration is primarily due to the ability of BECN1-defective tumor cells to overexpress and release CCL5 cytokine in the tumor microenvironment by a mechanism involving the activation of the MAPK8/JNK-JUN/c-Jun signaling pathway. Clinically, we reported a strong positive correlation between the expression of NK cell marker and CCL5 in human melanoma tumors and more importantly, a significant increased survival is found in melanoma patients expressing a high level of CCL5. Overall, these findings highlight the impact of targeting autophagy in breaking the immunosuppressive tumor microenvironment barrier, thus allowing the trafficking of cytotoxic NK cells into the tumor bed. This study underscore the importance of autophagy inhibition in tumors as a novel therapeutic strategy to fully exploit NK cells antitumor properties in clinical settings.

Original languageEnglish
Pages (from-to)730-732
Number of pages3
JournalAutophagy
Volume14
Issue number4
DOIs
Publication statusPublished - 3 Apr 2018

Keywords

  • Beclin 1
  • CCL5 cytokine
  • Immune infiltration
  • autophagy
  • cancer immunotherapy
  • immunotherapy
  • melanoma
  • natural killer cells

Fingerprint

Dive into the research topics of 'Targeting autophagy blocks melanoma growth by bringing natural killer cells to the tumor battlefield'. Together they form a unique fingerprint.

Cite this