Fig. 7: The combination of low-dose anlotinib with anti-PD–1 immune therapy may synergistically restructure the tumor immunosuppressive microenvironment. | Nature Communications

Fig. 7: The combination of low-dose anlotinib with anti-PD–1 immune therapy may synergistically restructure the tumor immunosuppressive microenvironment.

From: Sintilimab and anlotinib with gemcitabine plus cisplatin in advanced biliary tract cancer: SAGC a randomized phase 2 trial

Fig. 7: The combination of low-dose anlotinib with anti-PD–1 immune therapy may synergistically restructure the tumor immunosuppressive microenvironment.The alternative text for this image may have been generated using AI.

a-d Flow cytometry was carried out to analyze the population and composition of immune cells after administration of various treatment groups. The proportion of CD4+ T cells, CD8+ T cells, NK cells, and NKT cells in CD45+ immune cells (a). The proportion of effector T cells (b) and Tpex cells (c) in CD8+ T cells. The proportion of Tregs (d) in CD4+ T cells. The production of effector cytokines and the expression of immune suppressors in immune cells were measured by flow cytometry. MFI quantification analyses (left) and representative flow plots (right) of GZMB (e), perforin (f), TRAIL (g) and PD-1(h) in CD8+ T cells. MFI quantification analysis (left) and representative flow plots (right) of GZMB expression in NK cells (i). Additional results of immune cell subsets, effector cytokines in CD8+ T cells and effector cytokines in NK cells are illustrated in Supplementary Fig. S8. Gating procedures are described in Supplementary Figs. S9 and S10. n = 4 mice per group (a, e-i). n = 5 mice per group (b-d). Data are presented as mean ± SEM (a–i). Statistical significance was determined with one-way ANOVA followed by Holm-Sidak multiple comparison test. ns, no significance, *p  <  0.05, **p  <  0.01, ***p  <  0.001, versus control group (IgG group). Source data are provided as a Source Data file. Abbreviations: CCA cholangiocarcinoma, IgG control group, P anti-PD-1 therapy, A6 high-dose anlotinib (6 mg/kg), A3 low-dose anlotinib (3 mg/kg), A6 + P high-dose anlotinib (6 mg/kg) plus anti-PD-1 therapy, A3 + P low-dose anlotinib (3 mg/kg) plus anti-PD-1 therapy, HD injection hydrodynamic tail vein injection, NK cells natural killer cells, NKT natural killer T cell, Tpex precursor exhausted CD8 + T cells, Tregs regulatory T cells, MFI mean fluorescence intensity, GZMB granzyme B, TRAIL TNF-related apoptosis-inducing ligand, PD-1 programmed cell death 1. Source data are provided as a Source Data file.

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