Comprehensive Pan-Cancer Analyses of Immunogenic Cell Death as a Biomarker in Predicting Prognosis and Therapeutic Response

Abstract

Immunogenic cell death (ICD), a form of regulated cell death, is related to anticancer therapy. Due to the absence of widely accepted markers, characterizing ICD-related phenotypes across cancer types remained unexplored. Here, we defined the ICD score to delineate the ICD landscape across 33 cancerous types and 31 normal tissue types based on transcriptomic, proteomic and epigenetics data from multiple databases. We found that ICD score showed cancer type-specific association with genomic and immune features. Importantly, the ICD score had the potential to predict therapy response and patient prognosis in multiple cancer types. We also developed an ICD-related prognostic model by machine learning and cox regression analysis. Single-cell level analysis revealed intra-tumor ICD state heterogeneity and communication between ICD-based clusters of T cells and other immune cells in the tumor microenvironment in colon cancer. For the first time, we identified IGF2BP3 as a potential ICD regulator in colon cancer. In conclusion, our study provides a comprehensive framework for evaluating the relation between ICD and clinical relevance, gaining insights into identification of ICD as a potential cancer-related biomarker and therapeutic target.

Pan‐cancer analyses of immunogenic cell death‐derived gene signatures: Potential biomarkers for prognosis and immunotherapy

“…Moreover, we determined the prognostic and clinical value of the ICD score in pan‐cancer and discovered the relevance between the ICD score and immunotherapy response in the SKCM DFCI 2015 cohort. A recent pan‐cancer analysis obtained results akin to ours: the ICD score could predict patient prognosis and treatment response 26 . Our study, compared to this research, conducted a more in‐depth analysis of patient survival, immune microenvironment, and clinical features based on the subtypes of the ICD score.…”

“…We conducted univariate and multivariate Cox regression analyses, and generated a nomogram based on the independent risk factors: durable clinical benefit (PD_SD vs. PR_CR) and ICD score (high versus low) (Table 1 and to ours: the ICD score could predict patient prognosis and treatment response. 26 Our study, compared to this research, conducted a more in-depth analysis of patient survival, immune microenvironment, and clinical features based on the subtypes of the ICD score. In previous studies, the high-ICD subtype, derived from ICD genes, has been considered a protective factor for prognosis in HNSCC, lung adenocarcinoma, and ESCA, but a risk factor in pancreatic cancer and glioblastoma multiforme.…”