Exhausted CD8+ T cells can be rewired by STAT5 (Jessica Cross via Flickr).

The transcription factor TOX epigenetically imprints T-cell exhaustion. Beltra et al. sought to identify factors that may counteract TOX-mediated exhaustion and revealed that constitutive activation of STAT5 functionally reinvigorates exhausted CD8+ T cells by antagonizing TOX-mediated exhaustion programs and promoting a durable effector-like state with superior antitumor potential. Induction of STAT5 activity in exhausted T cells using an orthogonal IL2:IL2Rβ pair enhances intermediate exhausted T-cell accumulation upon anti–PD-L1 treatment, amplifying responses to this therapy. The data demonstrate the therapeutic potential of engaging STAT5 to reverse TOX-mediated CD8+ T-cell exhaustion.

Beltra J-C, …, Wherry EJ. Immunity 2023 December 12;56:2699–718.E11.

IL4 drives myeloid cells to an immunosuppressive phenotype (Jawahar Swaminathan and MSD staff at the EBI via Wikipedia).

The molecular drivers of the immunosuppressive phenotype of myeloid cells within the non–small cell lung cancer (NSCLC)...

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