FIGURE 2.

Effects of lenvatinib on infiltration of tcf1⁺ PD1⁺ CD8⁺ T cells in the TME and spleen in mice. A, Schematic of lenvatinib therapy. Hepa1‐6 cells were in situ inoculated into C57BL/6 mice on day 0, lenvatinib was intragastrically administered daily when the tumor volume reached 150 mm³ on day 9, and tumor samples were collected for analysis on days 13 and 17. B, Proliferative activities (marked by expression of Ki‐67) of PD1⁺ CD8⁺ T cells from spleen and tumor in the negative control (NC) group and lenvatinib group were analyzed. Data were expressed as mean ± SEM (n = 5). C, Phenotypes of exhausted PD1⁺ CD8⁺ T cells (marked by expression of TCF1 and TIM3) from tumor in the NC group and the lenvatinib group were analyzed. Data were expressed as mean ± SEM (n = 5). D, The total number of tumor‐infiltrating CD8⁺ T cells and the number of pTex cells were detected. Data were expressed as mean ± SEM (n = 5). E, Phenotypes of exhausted PD1⁺ CD8⁺ T cells (marked by expression of TCF1 and Ki‐67) from spleen in the NC group and the lenvatinib group were analyzed. Data were expressed as mean ± SEM (n = 5). F, Tumor‐killing functions of intermediate Tex cells (marked by expression of granzyme B) from tumor in the NC group and the lenvatinib group were analyzed. Data were expressed as mean ± SEM (n = 5). *p < 0.05; **p < 0.01; ***p < 0.001, ****p < 0.0001