Many conventional chemotherapeutics play an immune-modulating effect by inducing immunogenic cell death (ICD) in tumor cells. However, they hardly arouse strong antitumor immune response because the immunosuppressive lymphocytes are present in the tumor microenvironment. These immunosuppressive lymphocytes include regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). We used a low dose of doxorubicin (DOX) to induce ICD in combination with immune regulator 1-methyl-DL-tryptophan (1MT) to suppress indoleamine 2,3-dioxygenase and overcome Treg- and MDSC-associated immune suppression. By co-encapsulation of DOX and 1MT into a reduction-responsive polypeptide nanogel, the drugs were simultaneously released in the tumor cells and synergistically performed antitumor efficacy. After treatment, recruitment of Tregs and MDSCs was inhibited, and the frequency of tumor-infiltrating CD8⁺ T cells was remarkably enhanced. These results demonstrated that the chemoimmunotherapy strategy effectively suppressed tumor growth without causing evident adverse effects, indicating its great potential in clinical cancer therapy.

许多常规化学疗法通过在肿瘤细胞中诱导免疫原性细胞死亡 (ICD) 来发挥免疫调节作用。然而，由于肿瘤微环境中存在免疫抑制淋巴细胞，它们几乎不会引起强烈的抗肿瘤免疫反应。这些免疫抑制性淋巴细胞包括调节性 T 细胞 (Treg) 和髓源性抑制细胞 (MDSC)。我们使用低剂量的多柔比星 (DOX) 与免疫调节剂 1-甲基-DL-色氨酸 (1MT) 联合诱导 ICD，以抑制吲哚胺 2,3-双加氧酶并克服 Treg 和 MDSC 相关的免疫抑制。通过将 DOX 和 1MT 共包封到还原反应性多肽纳米凝胶中，药物同时释放到肿瘤细胞中并协同发挥抗肿瘤功效。治疗后，⁺ T 细胞显着增强。这些结果表明，化学免疫治疗策略有效地抑制了肿瘤的生长而没有引起明显的副作用，表明其在临床癌症治疗中的巨大潜力。