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Romero, Joan Miguel; Titmuss, Emma; Wang, Yifan; Vafiadis, James; Pacis, Alain; Jang, Gun Ho; Zhang, Amy; Golesworthy, Bryn; Lenko, Tatiana; Williamson, Laura M; Grünwald, Barbara; O'Kane, Grainne M; Jones, Steven J M; Marra, Marco A; Wilson, Julie M; Gallinger, Steven; Laskin, Janessa; Zogopoulos, George
NPJ precision oncology, 08/2023, Letnik: 7, Številka: 1Journal Article
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 ) 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 tumors displaying ≥10 mutations per megabase. In a heterogeneous pan-cancer cohort of 82 patients, with advanced and previously treated solid cancers, c-Score 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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