Immunogenic Apoptosis as a Novel Tool for Anticancer Vaccine Development

Abstract

Immunogenic apoptosis, or more appropriately called immunogenic cell death (ICD), is a recently described form of apoptosis induced by a specific set of chemotherapeutic drugs or by physical therapeutic modalities, such as ionizing irradiation and photodynamic therapy. The peculiar characteristic of ICD is the ability to favor recognition and elimination of dying tumor cells by phagocytes in association with the release of pro-inflammatory molecules (such as cytokines and high-mobility group box-1). While in vitro and animal models pointed to ICD as one of the molecular mechanisms mediating the clinical efficacy of some anticancer agents, it is hard to clearly demonstrate its contribution in cancer patients. Clinical evidence suggests that the induction of ICD alone is possibly not sufficient to fully subvert the immunosuppressive tumor microenvironment. However, interesting results from recent studies contemplate the exploitation of ICD for improving the immunogenicity of cancer cells to use them as an antigen cargo in the development of dendritic cell (DC) vaccines. Herein, we discuss the effects of danger signals expressed or released by cancer cells undergoing ICD on the maturation and activation of immature and mature DC, highlighting the potential added value of ICD in adoptive immunotherapy protocols.

Hypotonic stress enhances colon cancer cell death induced by platinum derivatives and immunologically improves antitumor efficacy of intraperitoneal chemotherapy

“…The importance of ICD in cancer treatment has been highlighted in several studies showing that cancer patients present mutations on genes coding for ICD stigmata receptors, such as TLR4 (one of the receptors of HMGB1) or P2X7 (the receptor of ATP) which can affect the response to treatment or have a significant negative prognostic impact on survival . Moreover, the expression of calreticulin on patient tumor cells is a prognosis marker . However, the relevance of cell death‐induced antitumor immune response was rarely proved in patients .…”

“…Moreover, the expression of calreticulin on patient tumor cells is a prognosis marker . However, the relevance of cell death‐induced antitumor immune response was rarely proved in patients . This can be explained either by the inability of chemotherapy to induce ICD or by their incapacity to reach efficient doses and/or time exposure of patient tumors.…”

Platinum Derivatives Effects on Anticancer Immune Response

“…Recognition of membrane-associated CRT by CD91 and CD69 on APCs (antigen-presenting cells-DCs, macrophages, neutrophils) favors the phagocytosis of apoptotic bodies and is required to initiate adaptive immune response [10]. Moreover, CRT expression on patient tumor cells is a prognosis marker [11]. Immunogenic cell death (ICD) characteristics.…”

HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer

“…Apoptosis, a form of programmed cell death, is pivotal for suppressing tumor growth and guaranteeing healthy tissue homeostasis . Targeting apoptosis pathways to induce cancer cell death has always been a high‐priority strategy for cancer therapy . The intrinsic (mitochondrial) apoptosis pathway is regulated by the BCL2 family members, which are usually dysregulated in cancers …”

“…10,11 Targeting apoptosis pathways to induce cancer cell death has always been a high-priority strategy for cancer therapy. 12,13 The intrinsic (mitochondrial) apoptosis pathway is regulated by the BCL2 family members, which are usually dysregulated in cancers. 10,14,15 In the study reported here, we found that HOXA10 was upregulated in GC tissues both at the mRNA and protein levels.…”