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IRF2 drives interferon-mediated CD8 T cell exhaustion to restrict anti-tumor immunity

Speaker: Sabelo Lukhele, PhD, Scientific Associate, Princess Margaret Cancer Centre, University Health Network

Type I interferons are central regulators for hallmarks of cancer but can also take on immunosuppressive roles that drive therapy resistance. Using a mouse model to analyze the immune landscape across diverse tumor types, Lukhele describes these opposing outcomes of interferon signaling.
Type I and II interferon signaling contributes to long-term tumor control mediated by IRF2 deficiency, with IRF2 as a feedback nexus transforming the pro-inflammatory effects of IFN-I into suppressive signaling. This strategy can further be tested in human CD8 T cells to enhance CAR T cell therapies.