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Updated: Jun 21, 2025
Immunophenotyping of Orthotopic Homograft Syngeneic of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
Published on: October 9, 2018
Pan-cell death-related signature reveals tumor immune microenvironment and optimizes personalized therapy
Linzhi Han1, Jingyi He1, Hongxin Xie1
1Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
Abstract:
This study constructed a comprehensive analysis of cell death modules in eliminating aberrant cells and remodeling tumor microenvironment (TME). Consensus analysis was performed in 490 lung adenocarcinoma (LUAD) patients based on 4 types of cell death prognostic genes. Intersection method divided these LUAD samples into 5 cell death risk (CDR) clusters, and COX regression analysis were used to construct the CDR signature (CDRSig) with risk scores. Significant differences of TME phenotypes, clinical factors, genome variations, radiosensitivity and immunotherapy sensitivity were observed in different CDR clusters. Patients with higher risk scores in the CDRSig tended to be immune-excluded or immune-desert, and those with lower risk scores were more sensitive to radiotherapy and immunotherapy. The results from mouse model showed that intense expression of the high-risk gene PFKP was associated with low CD8+ T cell infiltration upon radiotherapy and anti-PD-L1 treatment. Deficient assays in vitro confirmed that PFKP downregulation enhanced cGAS/STING pathway activation and radiosensitivity in LUAD cells. In conclusion, our studies originally performed a comprehensive cell death analysis, suggesting the importance of CDR patterns in reprogramming TME and providing novel clues for LUAD personalized therapies.
Insights
This study reveals how cell death patterns impact the tumor microenvironment (TME) in lung adenocarcinoma (LUAD). Lower cell death risk scores correlate with better sensitivity to radiotherapy and immunotherapy, offering new therapeutic strategies.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Aberrant cell elimination and tumor microenvironment (TME) remodeling are critical in cancer progression.
- Understanding cell death mechanisms is key to developing effective cancer therapies.
Purpose of the Study:
- To comprehensively analyze cell death modules in eliminating aberrant cells and remodeling the TME in lung adenocarcinoma (LUAD).
- To develop a cell death risk signature (CDRSig) for predicting patient outcomes and treatment sensitivity.
Main Methods:
- Consensus analysis of 4 types of cell death prognostic genes in 490 LUAD patients.
- Division of samples into 5 cell death risk (CDR) clusters using an intersection method.
- COX regression analysis to construct the CDRSig and assess its correlation with TME phenotypes, clinical factors, genomic variations, and treatment sensitivity.
Main Results:
- Significant differences in TME phenotypes, clinical factors, genomic variations, radiosensitivity, and immunotherapy sensitivity were observed across CDR clusters.
- Higher CDRSig risk scores were associated with immune-excluded or immune-desert phenotypes.
- Lower risk scores correlated with increased sensitivity to radiotherapy and immunotherapy.
Conclusions:
- Cell death patterns significantly influence TME reprogramming and patient responses to therapy in LUAD.
- The CDRSig provides novel insights into LUAD progression and offers potential for personalized treatment strategies.
- PFKP, a high-risk gene, may regulate TME infiltration and radiosensitivity via the cGAS/STING pathway.
