2022
DOI: 10.1038/s41586-022-04585-5
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CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours

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Cited by 236 publications
(185 citation statements)
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“…The requirement of IFN-γ in regulating the survival and function of M2 macrophage following PD-L1 blockade suggests that amplifying IFN-γ signaling may be an actionable target for improving the combination of CAR T cells and ICB. Recent studies have shown that IFN-γ production by CAR T cells is critical for tumor cell killing, 45 and in remodeling the TME alone and in combination with ICB. Various engineering and manufacturing approaches can modify IFN-γ secretion by CAR T cells.…”
Section: Discussionmentioning
confidence: 99%
“…The requirement of IFN-γ in regulating the survival and function of M2 macrophage following PD-L1 blockade suggests that amplifying IFN-γ signaling may be an actionable target for improving the combination of CAR T cells and ICB. Recent studies have shown that IFN-γ production by CAR T cells is critical for tumor cell killing, 45 and in remodeling the TME alone and in combination with ICB. Various engineering and manufacturing approaches can modify IFN-γ secretion by CAR T cells.…”
Section: Discussionmentioning
confidence: 99%
“…CAR T cells as effectors, NALM-6 tumor cells as targets, and pre-functionalized beads coated with IFN-γ capture antibody as cytokine sensors, were loaded sequentially onto a nanowell grid array, and the kinetics of killing and end-point cytokine secretion from the same cells was monitored using TIMING (Figure 1A-B, Supplementary Video 1). We chose to track IFN-γ because of the known impact of CAR T cell derived IFN-γ in shaping the susceptibility of tumors, enabling endogenous host immunity, and the potential for toxicity (17)(18)(19).…”
Section: Resultsmentioning
confidence: 99%
“…Responsiveness to IFNγ by stromal cells has been shown to be insufficient for IFNγ-induced tumor regression, whereas responsiveness of ECs to IFNγ is both necessary and sufficient (43). Moreover, preserved IFNγR pathway is required for CTL killing of tumor cells in GBM and other solid tumors (44). Analysis of IFNγ receptor expression by ECs under each therapeutic setting revealed that αPD1+A2V therapy induced significantly higher expression of IFNγR on ECs compared to other treatment conditions (Fig.…”
Section: Resultsmentioning
confidence: 99%