Alessandra Castiglioni, Yagai Yang, Katherine Williams, Alvin Gogineni, Ryan S Lane, Amber W Wang, Justin A Shyer, Zhe Zhang, Stephanie Mittman, Alan Gutierrez, Jillian L Astarita, Minh Thai, Jeffrey Hung, Yeqing Angela Yang, Tony Pourmohamad, Patricia Himmels, Marco De Simone, Justin Elstrott, Aude-Hélène Capietto, Rafael Cubas, Zora Modrusan, Wendy Sandoval, James Ziai, Stephen E Gould, Wenxian Fu, Yulei Wang, James T Koerber, Shomyseh Sanjabi, Ira Mellman, Shannon J Turley, Sören Müller
TGFβ signaling is associated with non-response to immune checkpoint blockade in patients with advanced cancers, particularly in the immune-excluded phenotype. While previous work demonstrates that converting tumors from excluded to inflamed phenotypes requires attenuation of PD-L1 and TGFβ signaling, the underlying cellular mechanisms remain unclear. Here, we show that TGFβ and PD-L1 restrain intratumoral stem cell-like CD8 T cell (TSCL ) expansion and replacement of progenitor-exhausted and dysfunctional CD8 T cells with non-exhausted T effector cells in the EMT6 tumor model in female mice...
August 5, 2023: Nature Communications