TGF-ß signaling suppresses tumor surveillance by inducing the differentiation of tumor associated NK cells into type 1 innate lymphoid cells

Avoiding destruction by immune cells is a hallmark of cancer, yet how tumors ultimately evade natural killer (NK) cell control remains incompletely defined. In this study we describe the conversion of NK cells (CD49a-CD49b+Eomes+) into intermediate type 1 innate lymphoid (intILC1) cell (CD49a+CD49b+Eomes+) and ILC1 (CD49a+CD49b-Eomes-) cell populations in the tumor microenvironment dependent on TGF-ß signaling. Strikingly, intILC1s/ILC1s were unable to control local tumor growth and metastasis, whereas NK cells favored tumor immune surveillance. Experiments using TNF-blocking antibodies suggested that innate immune escape was partially mediated by TNF-producing ILC1s. Together our data highlight the unexpected plasticity of group 1 ILCs in tumors and reveal a novel mechanism by which tumors escape innate immune surveillance. NOTE: this study previously had accession EGAS00001002514