Investigating the Immunogenic Cell Death-Dependent Subtypes and Prognostic Signature of Triple-Negative Breast Cancer

Phenomics. 2024 Mar 13;4(1):34-45. doi: 10.1007/s43657-023-00133-x. eCollection 2024 Feb.

Abstract

Recently, immunotherapy has emerged as a promising and effective method for treating triple-negative breast cancer (TNBC). However, challenges still persist. Immunogenic cell death (ICD) is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells. Nevertheless, the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood. In this study, we observed dysregulation of the ICD process and verified the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To investigate the potential role of the ICD process in TNBC progression, we determined the ICD-dependent subtypes, and two were identified. Analysis of their distinct tumor immune microenvironment (TIME) and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune "cold" and "hot" phenotypes, respectively. In addition, we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability. The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identification of targeted effective agents for individualized clinical strategies.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-023-00133-x.

Keywords: Immunogenic cell death; Prognostic signature; Triple-negative breast cancer; Tumor immune microenvironment.