Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients. (October 2022)

• Record Type: Journal Article
• Authors: Foy, Jean-Philippe; Karabajakian, Andy; Ortiz-Cuaran, Sandra; Boussageon, Maxime; Michon, Lucas; Bouaoud, Jebrane; Fekiri, Dorssafe; Robert, Marie; Baffert, Kim-Arthur; Hervé, Geneviève; Quilhot, Pauline; Attignon, Valéry; Girod, Angélique; Chaine, André; Benassarou, Mourad; Zrounba, Philippe; Caux, Christophe; Ghiringhelli, François; Lantuejoul, Sylvie; Crozes, Carole; Brochériou, Isabelle; Pérol, Maurice; Fayette, Jérôme; Bertolus, Chloé; Saintigny, Pierre
• Is Part Of: European journal of cancer. Volume 174(2022)
• Page Start: 287
• Page End: 298
• Publication Date: 2022-10
• Subjects: Head and neck cancer -- Non-small cell lung cancer -- Immune microenvironment -- Immunologically hot tumours -- Biomarker -- Immunotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.06.034
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Introduction: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours. Methods: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Results: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis. Conclusion: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors. Highlights: The 'HOT' score allows to identify immunologically active 'hot' tumours. Patients with hot tumours treated by PD1/PD-L1 inhibitors had improved survival. The immunologically 'hot' phenotype is stable between biopsy and surgical specimen. The HOT score is a promising biomarker evaluable from real-life FFPE samples.