Remarkably, cancer cell-intrinsic loss of IRE1α provoked potent antitumor immune responses by altering both the lymphoid and myeloid cell subsets in the TME, a new paradigm in NSCLC, consistent with emerging evidence in melanoma and glioblastoma showing that cancer cell-intrinsic pathways alter the immune landscape in the TME21–23. Here, ERN1 is linked to melanoma.