Amplifying "eat me signal" by immunogenic cell death for potentiating cancer immunotherapy

Abstract

Immunogenic cell death (ICD) is a unique mode of cell death, which can release immunogenic damage-associated molecular patterns (DAMPs) and tumor-associated antigens to trigger long-term protective antitumor immune responses. Thus, amplifying "eat me signal" during tumor ICD cascade is critical for cancer immunotherapy. Some therapies (radiotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), etc.) and inducers (chemotherapeutic agents, etc.) have enabled to initiate and/or facilitate ICD and activate antitumor immune responses. Recently, nanostructure-based drug delivery systems have been synthesized for inducing ICD through combining treatment of chemotherapeutic agents, photosensitizers for PDT, photothermal transformation agents for PTT, radiosensitizers for radiotherapy, etc., which can release loaded agents at an appropriate dosage in the designated place at the appropriate time, contributing to higher efficiency and lower toxicity. Also, immunotherapeutic agents in combination with nanostructure-based drug delivery systems can produce synergetic antitumor effects, thus potentiating immunotherapy. Overall, our review outlines the emerging ICD inducers, and nanostructure drug delivery systems loading diverse agents to evoke ICD through chemoradiotherapy, PDT, and PTT or combining immunotherapeutic agents. Moreover, we discuss the prospects and challenges of harnessing ICD induction-based immunotherapy, and highlight the significance of multidisciplinary and interprofessional collaboration to promote the optimal translation of this treatment strategy.

Keywords: drug delivery system; immune microenvironment; immunogenic cell death; immunotherapy; nanomedicine; synergetic treatment.