CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells

Abdul S. Qadir, Jean Philippe Guégan, Christophe Ginestier, Assia Chaibi, Alban Bessede, Emmanuelle Charafe-Jauffret, Manon Macario, Vincent Lavoué, Thibault de la Motte Rouge, Calvin Law, Jacob Vilker, Hongbin Wang, Emily Stroup, Matthew J. Schipma, Bryan Bridgeman, Andrea E. Murmann, Zhe Ji, Patrick Legembre, Marcus E. Peter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. In different genetically engineered mouse models tumor-expressed CD95 was shown to be critical for cell growth. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95 in metastatic triple negative breast cancer (TNBC) cells prevents tumor growth by modulating the immune landscape. CD95-deficient, but not wild-type, tumors barely grow in an immune-competent environment and show an increase in immune infiltrates into the tumor. This growth reduction is caused by infiltrating NK cells and does not involve T cells or macrophages. In contrast, in immune compromised mice CD95 k.o. cells are not growth inhibited, but they fail to form metastases. In summary, we demonstrate that in addition to its tumor and metastasis promoting activities, CD95 expression by tumor cells can exert immune suppressive activities on NK cells, providing a new target for immune therapy.

Original languageEnglish (US)
Article number103348
JournaliScience
Volume24
Issue number11
DOIs
StatePublished - Nov 19 2021

Keywords

  • Cancer
  • Cell biology
  • Immunology

ASJC Scopus subject areas

  • General

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