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. 2020 Dec 22;1(9):100160. doi: 10.1016/j.xcrm.2020.100160

Figure 6.

Figure 6

Chemomodulation of Immune Susceptibility

(A and B) Response of (A) a PD-L1-;Gal9+ CRLM and (B) a PD-L1−;Gal9− CRLM to combination chemo-immunotherapies. Tumor slices (n = 3 per group) were treated with indicated drugs for 72 h, and the percentage of change in MTS absorbance (mean ± SD) was tabulated. Baseline expression of PD-L1 and galectin-9 was determined by IHC (right panels, original magnification 200×, scale bar, 100 μm). STS, staurosporine (positive control).

(C) DMSO negative control; α-PD1 and α-TIM3 represent blocking antibodies targeting the respective immune checkpoints. ∗p < 0.5 and ∗∗p < 0.001 compared to control, C. #p < 0.05. Clinical features of these 2 cases are shown in Figure S6D.

(C) Models of the effects of chemotherapy in the 2 types of CRLM. Left panel: CRLM with stem-like features expresses PD-1 ligands to evade immune surveillance. FI induces an IFN response along with the suppression of PD-L1 to enhance anti-tumor immune response. Right panel: CRLM with enterocyte-like phenotype expresses TIM-3 ligands, which is further augmented (by FI) or maintained (by FX) with chemotherapy to enforce immune evasion; this is reversible by α-TIM3 blocking antibodies to enhance anti-tumor effects.