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

ABSTRACT: Summary 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. Graphical abstract Highlights • CD95 expression promotes primary TNBC growth in immune-competent mice• CD95 KO TNBC cells do not metastasize in immune-deficient mice• Loss of CD95 triggers a pro-inflammatory program affecting the immune landscape• Loss of CD95 causes tumor destruction by NK cells in immune-competent mice Immunology; Cell biology; Cancer

SUBMITTER: Qadir A 

PROVIDER: S-EPMC8593563 | biostudies-literature |

REPOSITORIES: biostudies-literature