Fig. 6: Positive feedback loop between T-bet⁺ T cells and PD-L1⁺ tumor cells drives ICIs susceptibility.

a T-bet⁺-PD-L1⁺ niches are present in patients with rich infiltration of T-bet⁺ CD8⁺ T cells (GC-44). b Schematic graph of neighboring cells of T-bet^- CD8⁺ T cells and T-bet⁺ CD8⁺ T cells. Neighboring cells were defined as cells with a distance closer than 50um to the original cell. Orange denotes PD-L1⁺ cells, and blue denotes PD-L1- cells. c Box plots of mean PD-L1 intensity of the neighboring cells of T-bet⁺ CD8⁺ T cells, T-bet^- CD8⁺ T cells, T-bet⁺ CD4⁺ T cells, and T-bet^- CD4⁺ T cells in the GC cohort (T-bet⁺ CD8⁺ T cells vs. T-bet^- CD8⁺ T cells, P = 0.015; T-bet⁺ CD4⁺ T cells vs. T-bet^- CD4⁺ T cells, P = 2.06e-15, two-tailed Mann-Whitney U test). d Selection of ROIs in the TME of an ICI responder (ICI-12). T-bet⁺-PD-L1⁺ niches were identified using adjacent mIHC images (staining for T-bet, CD4, CD8, PD-1, PD-L1, pan-CK, and dapi). e Expression of MSS-PR-related genes (CXCL9, CXCL10, CCL3, CCL5, IFNG, GZMB, CXCR3, and IDO1) from the centers to the edges of T-bet⁺-PD-L1⁺ niches. Four niches were taken from an ICI responder (ICI-12), and another four were taken from an MSS-PR patient (GC-97). f Schematic graph of positive feedback loop between T-bet⁺ T cells and PD-L1⁺ tumor cells (Created in BioRender. Tang, Shiying. (2025): https://biorender.com/o50y390; https://biorender.com/d93b442; https://biorender.com/n49h689; https://biorender.com/c07s866). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns is abbreviation for not significant.