Microbes mediated immunogenic cell death in cancer immunotherapy

Abstract

SummaryImmunogenic cell death (ICD) is one of the 12 distinct cell death forms, which can trigger immune system to fight against cancer cells. During ICD, a number of cellular changes occur that can stimulate an immune response, including the release of molecules called damage‐associated molecular patterns (DAMPs), signaling to immune cells to recognize and attack cancer cells. By virtue of their pivotal role in immune surveillance, ICD‐based drug development has been a new approach to explore novel therapeutic combinations and personalized strategies in cancer therapy. Several small molecules and microbes can induce ICD‐relevant signals and cause cancer cell death. In this review, we highlighted the role of microbe‐mediate ICD in cancer immunotherapy and described the mechanisms through which microbes might serve as ICD inducers in cancer treatment. We also discussed current attempts to combine microbes with chemotherapy regimens or immune checkpoint inhibitors (ICIs) in the treatment of cancer patients. We surmise that manipulation of microbes may guide personalized therapeutic interventions to facilitate anticancer immune response.

Advances in tumor immunomodulation based on nanodrug delivery systems

“…Compared with other therapies, DAMPs released by ICD inducers can mobilize immune stimulation, promote the maturation of DCs, and activate T cells, thus achieving a positive tumor chemoimmunotherapy effect (67). According to their ability to activate cell death or release DAMPs, ICD inducers can be divided into two different categories: type I and type II (68). Type I ICD inducers do not induce tumor cell death by increasing endoplasmic reticulum stress, but the effects of lateral endoplasmic reticulum stress produce immunogenicity; type II ICD inducers selectively target the endoplasmic reticulum and release danger and apoptosis signaling molecules because of ROSdependent endoplasmic reticulum stress.…”

Mechanisms of programmed cell death

“…Immunogenic cell death is not only induced by drugs but can also occur in the context of radiation therapy, 12 photodynamic, and photothermal therapy, 13 as well upon infection by microbes including oncolytic viruses 14 . Logically, attempts are underway to create novel galenic formulation including nanoparticle‐based drug delivery systems to administer drugs that induce immunogenic cell death in tumors, yet do not mediate any systemic effects 13,15 .…”

“…Immunogenic cell death is not only induced by drugs but can also occur in the context of radiation therapy, 12 photodynamic, and photothermal therapy, 13 as well upon infection by microbes including oncolytic viruses. 14 Logically, attempts are underway to create novel galenic formulation including nanoparticle-based drug delivery systems to administer drugs that induce immunogenic cell death in tumors, yet do not mediate any systemic effects. 13,15 Interestingly, cell death of cancer cells can be accompanied by the release of nanoscale extracellular vesicles dubbed exosomes that constitute potential biomarkers of ongoing cell death events and establish short-and long-distance communication with neighboring cells and distant tissues.…”