Prerequisites for the antitumor vaccine-like effect of chemotherapy and radiotherapy

For a long time, anticancer therapies were believed to work (and hence convey a therapeutic benefit) either by killing cancer cells or by inducing a permanent arrest in their cell cycle (senescence). In both scenarios, the efficacy of anticancer regimens was thought to depend on cancer cell-intrinsic features only. More recently, the importance of the tumor microenvironment (including stromal and immune cells) has been recognized, along with the development of therapies that function by modulating tumor cell-extrinsic pathways. In particular, it has been shown that some chemotherapeutic and radiotherapeutic regimens trigger cancer cell death while stimulating an active immune response against the tumor. Such an immunogenic cell death relies on the coordinated emission of specific signals from dying cancer cells and their perception by the host immune system. The resulting tumor-specific immune response is critical for the eradication of tumor cells that may survive therapy. In this review, we discuss the molecular mechanisms that underlie the vaccine-like effects of some chemotherapeutic and radiotherapeutic regimens, with particular attention to the signaling pathways and genetic elements that constitute the prerequisites for immunogenic anticancer therapy.