{"entity":{"id":"interferon-gamma-signature","kind":"term","name":"Interferon-gamma gene signature (T-cell-inflamed signature)","aka":["IFN-gamma signature","interferon gamma signature","IFNG signature","T-cell-inflamed gene expression profile","T cell-inflamed GEP","18-gene GEP","inflamed signature","hot tumour signature","immune gene signature","GEP score","Tumor Inflammation Signature"],"tldr":"An interferon-gamma signature is a readout of a handful of genes that T cells switch on when they are already inside a tumour and fighting; tumours with a high score respond to PD-1 drugs more often across many cancer types, but the score is not yet reliable enough to use outside trials.","summary":"What is measured: RNA expression of interferon-gamma-responsive and T-cell genes such as IFNG, CXCL9, CXCL10, CXCL11, IDO1, STAT1, HLA-DRA, PRF1, GZMB and CD8A. How: NanoString or RNA sequencing of tumour tissue; the 18-gene T-cell-inflamed gene expression profile of Ayers and colleagues (2017) was derived in pembrolizumab-treated patients and correlates with PD-L1 immunohistochemistry and tumour-infiltrating lymphocytes but adds to tumour mutational burden, the two being largely independent (Cristescu, Science 2018). A high score tracks higher response rates and longer progression-free survival to pembrolizumab across the KEYNOTE programme and to nivolumab with ipilimumab in melanoma; in the neoadjuvant NADINA trial almost every patient with a high score had a major pathological response and could skip adjuvant therapy. What a result changes: nothing in routine care yet; it stratifies trials, defines biomarker-guided arms (including follow-on trials that adapt adjuvant therapy to the score), and identifies cold tumours for combination strategies; it does not predict benefit from chemotherapy or anti-VEGF drugs. Where it matters: melanoma, advanced and stage III.","asOf":"2026-09-17","links":[],"tags":[],"related":["pd-l1-testing","tmb","tils","gene-expression","pembrolizumab","nivolumab","ipilimumab","rna-seq","major-pathological-response"],"cancers":["melanoma","advanced-melanoma","stage-iii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/interferon-gamma-signature/","neighbours":{"term":[{"id":"gene-expression","kind":"term","name":"Gene expression","route":"/terms/gene-expression/"},{"id":"major-pathological-response","kind":"term","name":"Major pathological response (MPR)","route":"/terms/major-pathological-response/"},{"id":"pd-l1-testing","kind":"term","name":"PD-L1 expression testing (22C3, SP142, SP263)","route":"/terms/pd-l1-testing/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"},{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"drug":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"stage-iii-melanoma","kind":"cancer","name":"Stage III melanoma (after surgery)","route":"/cancers/stage-iii-melanoma/"}]}}