Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors

A Castiglioni, Y Yang, K Williams, A Gogineni… - Nature …, 2023 - nature.com
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 …

486 Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors

K Williams, A Castiglioni, Y Yang, A Gogineni… - 2023 - jitc.bmj.com
Background TGFβ signaling is associated with non-response to immune checkpoint
blockade in patients with advanced metastatic cancers, particularly in patients with 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 largely unclear. Methods We performed single-
cell RNA-seq (n= 5 animals per treatment) on myeloid, stromal, tumor, and T cells, as well as …
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