Immunogenic Cell Death: An Emerging Target in Gastrointestinal Cancers

Abstract

Immunogenic cell death (ICD) is a regulated form of cell death that induces the activation of both innate and adaptive immune responses through the release of damage-associated molecular patterns (DAMPs) and their subsequent recognition by pattern-recognition receptors (PRRs), generating specific CD8+ T lymphocytes. Thus, ICD inducers (such as certain chemotherapeutic agents, targeted therapies, radiation, and oncolytic viruses) could become a potential cancer treatment by providing antitumour immunity and cancer vaccination. Moreover, their combination with immunotherapy, especially with immune checkpoint inhibitors, could overcome the immunosuppressive tumour microenvironment that characterises certain cancers, including gastrointestinal cancers. This review will provide insights into the role of ICD induction in colorectal, gastric, pancreatic, and hepatocellular carcinomas. Specifically, we will discuss the main mechanisms involved in ICD, their potential application in gastrointestinal cancer treatment, and the latest clinical trial updates.

Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosis

“…Although gastric cancer (GC) incidence and mortality have decreased in recent decades, GC remains one of the greatest tumor burdens and the third most common reason for cancer-related deaths globally ( Siegel et al, 2022 ). In spite of recent breakthroughs in therapeutic modalities and immunotherapy reagents, treating locally progressed and metastatic GC is still problematic and challenging ( Yu et al, 2019 ; Chiaravalli et al, 2022 ). According to the latest evidence, preoperative radiation (RT) for GC can have a favorable therapeutic effect, although the adjuvant RT has proven otherwise ( Lee et al, 2021 ; Lordick et al, 2021 ).…”

Immunogenic cell death-associated biomarkers classification predicts prognosis and immunotherapy efficacy in pancreatic ductal adenocarcinoma

“…A comprehensive literature review that discovered the ICD-related genes earlier was published by Chiaravalli ( 4 ). To further illuminate the relationships between these ICD-related genes, we carried out protein-protein interaction (PPI) network analysis using the STRING database ( Figure 1A ).…”

“…Chiaravalli et al. ( 4 ) have previously detailed the genes associated with ICD that were examined in our investigation. In summary, ICD parameters were found by doing a thorough literature search (using Scopus, Web of Knowledge, and PubMed for relevant research studies conducted in vitro using primary human immune cells and/or in vivo using mice).…”

“…They have the capacity to mobilize antigen-presenting cells (APCs) and activate T cells to elicit adaptive immune responses against tumor antigens. Then, tumor-specific immune responses may be triggered, directly destroying tumor cells or triggering anti-tumor immunity, increasing the long-term efficacy of anticancer drugs ( 3 , 4 ). Due to its immunogenicity, the immune system’s activation in tumors, and the production of several tumor antigens, ICD is anticipated to offer fresh concepts and approaches for anti-tumor immunotherapy ( 5 ).…”

Ghost messages: cell death signals spread

“…For example, near‑infrared photoimmunotherapy induced cell death enhances DCs migration via ATP-P2X7 and HMGB1-TLR4 pathway in colon adenocarcinoma-bearing mice [ 203 ]. In addition, immunogenic cell death inducer oxaliplatin has been widely used in the treatment of colorectal, gastric, and pancreatic cancers [ 204 ]. Consequently, treatments aiming at immunogenic cell death targets and strengthening antitumor immune response will greatly improve clinical outcomes.…”