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• W4385700132 abstract "Abstract Immune checkpoint inhibitors (ICI) are highly effective in specific cancers where canonical markers of antitumor immunity are used for patient selection. Improved predictors of T cell-inflammation are needed to identify ICI-responsive tumor subsets in additional cancer types. We investigated associations of a 4-chemokine expression signature (c-Score: CCL4 , CCL5 , CXCL9 , CXCL10 ) with metrics of antitumor immunity across tumor types. Across cancer entities from The Cancer Genome Atlas, subgroups of tumors displayed high expression of the c-Score (c-Score hi ) with increased expression of immune checkpoint (IC) genes and transcriptional hallmarks of the cancer-immunity cycle. There was an incomplete association of the c-Score with high tumor mutation burden (TMB), with only 15% of c-Score hi tumors displaying ≥10 mutations per megabase. In a heterogeneous pan-cancer cohort of 82 patients, with advanced and previously treated solid cancers, c-Score hi tumors had a longer median time to progression (103 versus 72 days, P = 0.012) and overall survival (382 versus 196 days, P = 0.038) following ICI therapy initiation, compared to patients with low c-Score expression. We also found c-Score stratification to outperform TMB assignment for overall survival prediction (HR = 0.42 [0.22–0.79], P = 0.008 versus HR = 0.60 [0.29-1.27], P = 0.18, respectively). Assessment of the c-Score using the TIDE and PredictIO databases, which include ICI treatment outcomes from 10 tumor types, provided further support for the c-Score as a predictive ICI therapeutic biomarker. In summary, the c-Score identifies patients with hallmarks of T cell-inflammation and potential response to ICI treatment across cancer types, which is missed by TMB assignment." @default.
• W4385700132 created "2023-08-10" @default.
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• W4385700132 date "2023-08-09" @default.
• W4385700132 modified "2023-10-11" @default.
• W4385700132 title "Chemokine expression predicts T cell-inflammation and improved survival with checkpoint inhibition across solid cancers" @default.
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• W4385700132 doi "https://doi.org/10.1038/s41698-023-00428-2" @default.
• W4385700132 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37558751" @default.
• W4385700132 hasPublicationYear "2023" @default.
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