Differential PD-1 inhibitor efficacy among different mouse tumor models

  Objective  To explore the different responses to PD-1 (programmed death-1) inhibitor in different mouse tumor models.

  Methods  Mouse tumor models, including B16 melanoma, CT26 colon cancer, MC38 colon cancer, were established. B16 melanoma and CT26 colon cancer tumor models were divided into control group and PD-1 inhibitor treatment group, and MC38 colon cancer tumor model was divided into four groups, control group, PD-1 inhibitor treatment group, high dose PD-1 inhibitor treatment group and delayed PD-1 inhibitor treatment group. Tumor size data in each group was recorded, tumor growth and survival curve were drawn. The tumor infiltrating CD8⁺ T lymphocytes were sorted by CD8 beads and the quantitative differences were analyzed. The tumor infiltrating T lymphocyte subsets were measured by flow cytometry to explore the types of immune cells related to the anti-tumor activity of PD-1 inhibitor.

  Results  PD-1 inhibitor had no anti-tumor efficacy in CT26 colon tumor model, and minor anti-tumor efficacy in B16 melanoma tumor model; but significant anti-tumor efficacy in MC38 colon tumor model. The efficacy varied by treatment duration and dose of PD-1 inhibitor in MC38 colon tumor model. After PD-1 inhibitor treatment, the absolute number of tumor infiltrating CD8⁺ T lymphocytes increased, and the proportion of CD8⁺ Ki67⁺, CD8⁺ IFN-γ⁺, CD8⁺ Ki67⁺ IFN-γ⁺ tumor infiltrating T lymphocytes all increased (P < 0.05, respectively).

  Conclusion  MC38 colon tumor model is appropriate to study the anti-tumor efficacy of PD-1 inhibitor; PD-1 inhibitor can promote the proliferation and function of tumor infiltrating CD8⁺ T cells and enhance the anti-tumor immune response.