TNF and cancer: In summary, Bianchi and colleagues demonstrates that cell-autonomous Cxcl1, regulated by KRAS-TP53 genomic co-alteration in PDAC, mediates T-cell restriction through interactions with CXCR2+ neutrophilic MDSCs, and that TNF signaling in cancer cell-neutrophil crosstalk drives stromal inflammation, immune tolerance, and therapeutic resistance (Fig. 1).