Cytokines in immunogenic cell death: Applications for cancer immunotherapy

Abstract

Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis.

CD47 agonist peptide PKHB1 induces immunogenic cell death in T‐cell acute lymphoblastic leukemia cells

“…Similar results were obtained using doxorubicin in a mouse colon carcinoma (CT26) cell line . The use of this vaccine helps to stimulate anticancer immunity through the maturation of DC and cytotoxic T‐cell activation as well as enhancing NK cytotoxic activity …”

“…The increased immunogenicity of tumor cells triggers antitumor immune responses that could offer long‐term therapeutic effects . The finding that certain drugs are able to induce the awakening of the immune response by releasing DAMP and generating ICD triggered investigations to look for these types of agent . Anthracyclines, platinum derivatives, alkylating agents, and proteasome inhibitors are chemotherapeutic drugs with large amounts of evidence for triggering ICD .…”

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

“…Thus, giving preoperative chemotherapeutic agents phenotypically activated liver NK cells; however, the underlying mechanism remains unclear. This seems consistent with a previous finding that dying tumor cells treated with chemotherapeutic agents release proinflammatory cytokines that are crucial in the stimulation of protective anti‐cancer immune responses 45. Thus, it is possible that neoadjuvant chemotherapy enhances NK cell‐mediated cytotoxicity against tumor cells; however, we could not demonstrate the enhancement of cytotoxic activity in our experimental system.…”

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

“…136,147,150,151 Additional details about ICD-associated signaling pathways and resistance mechanisms can be found in various publications from us and others. [2][3][4]7,40,[152][153][154][155] Of note, only a limited number of cell death inducers can elicit bona fide ICD, and this capacity cannot be predicted on the basis of structural or functional similarities. Thus, while cisplatin and oxaliplatin both induce RCD at least in part by forming interand intra-strand DNA adducts, 156 only the latter induces ICD.…”