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Loss of major histocompatibility complex MHC-I expression contributes to cancer immune evasion. Here, the authors show that, in both mice and humans, MHC-I downregulation is associated with the induction of NK-cell exhaustion and that IL-21 restores NK-cell function and inhibits tumours progression.
IFNγ secretion by CD8+ T cells is critical for immunotherapy efficacy. In this study, the authors show that melanoma patients can become resistant to immunotherapy by acquiring chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2.
Tumour repopulating cells (TRC) are stem-like cells that can escape immune-mediated killing. Here, the authors show IFN-γ results in either dormancy or apoptosis of TRC depending on the activation of the IDO1 metabolic pathway, and that combining IFN-γ with IDO1 inhibitors results in enhanced tumour regression.