Figure 1.

The synergistic effect of different doses of platinum compounds combined with anti-PD-1 antibodies in the established MC38 model. (A) The effect and toxicity of different doses of Cis or Oxa in MC38 tumor-bearing mice. C57BL/6 mice were subcutaneously inoculated on day 0 with 5×10⁵ viable MC38 cells. When the mean tumor length reached approximately 4-8 mm (day 6), the mice were randomized by tumor size and intraperitoneally injected with single dose (0, 10, 20, 40 or 80 mg/kg) of platinum compounds (Cis, left panel; Oxa, right panel). The mean tumor lengths and survival rates of mice in each group (n = 5) are shown. Each symbol represents the mean ± SD of 5 mice. (B) Lymphocyte numbers and the frequency of CD4 or CD8 T cells within the lymphocyte population in the peripheral blood was detected by cell number quantification and flow cytometry on day 3 after platinum chemotherapy (n = 5). (C) Treatment schedule of MC38 tumor-bearing mice comparing platinum chemotherapy alone and sequential combination therapy with anti-PD-1 antibodies. MC38 tumor-bearing mice were intraperitoneally administered with Cis or Oxa (0, 5, 10 or 20 mg/kg) on day 6, and then 250 μg of anti-PD-1 (clone G4) or irrelevant hamster IgGs was sequentially injected every four days for a total of three times (days 9, 13 and 17). (D, E). The time-course of tumor growth in different groups. MC38 tumors on the right flank were treated with different doses of Cis (D) or Oxa (E) alone, or drugs combined with anti-PD1 antibodies, as described in (C). Tumors on the right flank were monitored (n = 4-5), and each line represents an individual mouse. Con: isotype antibody control; Cis: cisplatin; Oxa: oxaliplatin; anti-PD-1: anti-PD-1 antibodies. All results shown are representative of at least two independent experiments. Ns, no significant difference; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.