GSE109031
Gene expression profiling of sarcoma T cells deriving from Csf3r WT and KO mice
Recently, tumor-associated neutrophils (TANs) are considered as an important component of the tumor microenvironment. Here, we show that a specific genetic deficiency of neutrophils induced accelerated mesenchymal carcinogenesis associated with a deficient production of IFN-? in the tumor microenvironment. Unexpectedly, increased susceptibility to cancer of neutropenic mice was associated with impaired type 1 polarization of unconventional T cell (UTC) subsets, namely mucosal-associated invariant T (MAIT) cells and double CD4 and CD8 negative TCRß+ T (DNT) cells, resulting in reduced expression of T-bet and IFN-? and increased expression of Ror?t and IL-17A. Here, we uncovered a new mechanism by which neutrophils induced an IL-12-dependent type 1 polarization of MAIT and DNT cells characterized by the upregulation of T-bet expression. Therefore, a systemic reconstitution of Csf3r-/- mice with functional naïve neutrophils was sufficient to restore UTCs activation state and to slow down sarcoma growth. Finally, in patients with undifferentiated pleomorphic sarcoma, TAN infiltration signature was associated with better overall survival and increased expression of IFN-? and type 1 inflammatory response signature. Overall design: Transcriptome profiling of sarcoma associated T cells (CD4, CD8, UTCs, ?d) in Csf3r WT and KO mice