Fig 2: MET maintains PD-L1 expression in PDAC cells. A and B Human BXPC3 (A) and mouse KPC (B) PDAC cell lines are transfected with MET-silenced (shMET) and negative control (CTRL) vectors, respectively; MET and PD-L1 levels are assessed by immunoblotting. C Cell-surface PD-L1 expressions as assessed by flow cytometry in BXPC3 cells (up), with quantification (down). D Cell-surface PD-L1 expressions as assessed by flow cytometry in KPC cells (up), with quantification (down). E and F PD-L1 expressions as assessed by Western blotting analysis in BXPC3 (E) and KPC (F) cells after a dose-increasing treatment with capmatinib. G and H Endogenous co-immunoprecipitation of BXPC3 cells (G) and KPC cells (H) by MET and PD-L1 antibodies. MET and PD-L1 expression levels are analyzed by Western blotting

Fig 3: Synergistic effects of PD-L1 monoclonal antibody and MET inhibition in a subcutaneous mouse model. A Drug treatment protocol for capmatinib and PD-L1 antibody in C57/BL6 mice. At the endpoint, tumors were extracted and assessed via flow cytometry. B-E Sizes of subcutaneous KPC tumors in C57/BL6 mice treated with capmatinib and/or PD-L1 antibody. Mouse body weights (B), representative tumor images (C), tumor volumes (D), and tumor weights (E) are shown. F-G Quantification of CD3 + T cells (F) and CD8 + T cells (G) from purified tumor-infiltrating lymphocytes

Fig 4: Kaplan-Meier curves comparing OS rates between the high and low expression groups of PD-L1, PD-1, CD155 and TIGIT. SCLC patients with higher PD-L1 expression (PD-L1-high group) tended to have a shorter OS (16.26±2.91 months) compared with the PD-L1-low group (36.43±6.46 months; P=0.001). SCLC patients with higher CD155 expression (CD155-high group) tended to have a shorter OS (16.20±2.42 months) compared with the CD155-low group (29.87±3.66 months; P=0.002). Furthermore, patients were divided into three groups based on the expression levels of CD155 and PD-L1. The OS of SCLC patients with PD-L1 or CD155 overexpression (26.70±6.99 months) tended to be shorter compared with patients with low expression levels of both (38.82±2.67 months), and the OS of patients who had high expression levels of PD-L1 and CD155 was poorest (13.13±2.53 months) (P<0.001). In the PD-1 and TIGIT high or low expression groups, there were no significant associations with survival time. Low or high-censored indicates censored data in the low/high expression groups. These censored data represent patients with SCLC who were lost to follow-up or still alive at the end of the follow-up time. CD, cluster of differentiation; PD, programmed death; PD-L, programmed death ligand; TIGIT, T cell immunoreceptor with immunoglobulin and ITIM domains; SCLC, small cell lung cancer; OS, overall survival.

Fig 5: N2-like neutrophils are related to tumor sensitivity to DOX and tumor secondary immunity and immune memory. (A) Tumor weight (n = 6). (B) Tumor tissue permeability to Evans blue (n = 6). (C) Neutrophil to lymphocyte ratio (NLR) in peripheral blood in tumor-bearing mice (n = 6). (D) Bone marrow neutrophil immunophenotypes indicated by immunofluorescence (n = 6, 40×). (E) Spleen cytotoxic CD8+ cell rate (n = 6, 40×). (F) Tumor growth curve in a tumor rechallenge immune study. (n = 6). (G) Bone marrow neutrophil immunophenotypes indicated by immunofluorescence (n = 6, 40×). (H) Tumor tissue permeability to Evans blue (n = 6). (I) NLR in peripheral blood (n = 6). (J) Serum PD-L1 levels (n = 6). (K) Spleen tissue PD-1 expression indicated by immunofluorescence. (n = 5, 40×). (L) Spleen memory CD8+ cell rate (n = 6). The data present mean ± SD, the experiments were repeated three times, and statistical significance was determined by a t-test. *P < 0.05, **P < 0.01 vs. control; #P < 0.05, ##P < 0.01 vs. DOX. DOX, doxorubicin; BER, berberine.