抑制拓扑异构酶 I 通过诱导单核细胞衍生的树突状细胞来塑造抗肿瘤免疫

Understanding the rationale of combining immunotherapy and other anticancer treatment modalities is of great interest because of interpatient variability in single-agent immunotherapy.

Here, we demonstrated that topoisomerase I inhibitors, a class of chemotherapeutic drugs, can alter the tumor immune landscape, corroborating their antitumor effects combined with immunotherapy.

We observed that topotecan-conditioned TC-1 tumors were occupied by a vast number of monocytic cells that highly express CD11c, CD64, and costimulatory molecules responsible for the favorable changes in the tumor microenvironment.

Ly6C + MHC-II + CD11c hi CD64 hi cells, referred to as topotecan-induced monocyte-derived dendritic cells (moDCs), proliferate and activate antigen-specific CD8 + T cells to levels equivalent to those of conventional DCs. Phenotypic changes in Ly6C + cells towards moDCs were similarly induced by exposure to topotecan in vitro, which was more profoundly facilitated in the presence of tumor cells.

Notably, anti-M-CSFR reversed the acquisition of DC-like properties of topotecan-induced moDCs, leading to the abolition of the antitumor effect of topotecan combined with a cancer vaccine. In short, topoisomerase I inhibitors generate monocyte-derived antigen-presenting cells in tumors, which could be mediated by M-CSF-M-CSFR signaling.