# Interferon-gamma gene signature (T-cell-inflamed signature)

Source: https://onco.cc/terms/interferon-gamma-signature/  
OnCo record `interferon-gamma-signature` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: 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

## Connected records

- terms: [Gene expression](https://onco.cc/terms/gene-expression/), [Major pathological response (MPR)](https://onco.cc/terms/major-pathological-response/), [PD-L1 expression testing (22C3, SP142, SP263)](https://onco.cc/terms/pd-l1-testing/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/), [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- drugs: [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/), [Stage III melanoma (after surgery)](https://onco.cc/cancers/stage-iii-melanoma/)

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