Inflammatory response signature score model for predicting immunotherapy response and pan-cancer prognosis.

Background: Inflammatory responses influence the outcome of immunotherapy and tumorigenesis by modulating host immunity. However, systematic inflammatory response assessment models for predicting cancer immunotherapy (CIT) responses and survival across human cancers remain unexplored. Here, we investigated an inflammatory response score model to predict CIT responses and patient survival in a pan-cancer analysis. Methods: We retrieved 12 CIT response gene expression datasets from the Gene Expression Omnibus database (GSE78220, GSE19423, GSE100797, GSE126044, GSE35640, GSE67501, GSE115821 and GSE168204), Tumor Immune Dysfunction and Exclusion database (PRJEB23709, PRJEB25780 and phs000452.v2.p1), European Genome-phenome Archive database (EGAD00001005738), and IMvigor210 cohort. The tumor samples from six cancers types: metastatic urothelial cancer, metastatic melanoma, gastric cancer, primary bladder cancer, renal cell carcinoma, and non-small cell lung cancer.We further established a binary classification model to predict CIT responses using the least absolute shrinkage and selection operator (LASSO) computational algorithm. Findings: The model had high predictive accuracy in both the training and validation cohorts. During sub-group analysis, area under the curve (AUC) values of 0.82, 0.80, 0.71, 0.7, 0.67, and 0.64 were obtained for the non-small cell lung cancer, gastric cancer, metastatic urothelial cancer, primary bladder cancer, metastatic melanoma, and renal cell carcinoma cohorts, respectively. CIT response rates were higher in the high-scoring training cohort subjects (51%) than the low-scoring subjects (27%). The five-year survival rates in the high- and low score groups of the training cohorts were 62% and 21%, respectively, while those of the validation cohorts were 54% and 22%, respectively ( Conclusion: In this study, we developed an inflammatory response gene signature model that predicts patient survival and immunotherapy response in multiple malignancies. We further found that the predictive performance in the non-small cell lung cancer and gastric cancer group had the highest value among the six different malignancy subgroups. When compared with existing signatures, the inflammatory response gene signature scores for on-treatment samples were more robust predictors of the response to CIT in metastatic melanoma.