Polypeptide nanoformulation-induced immunogenic cell death and remission of immunosuppression for enhanced chemoimmunotherapy

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.