Jean-Philippe Foy1, Andy Karabajakian2, Sandra Ortiz-Cuaran3, Maxime Boussageon4, Lucas Michon3, Jebrane Bouaoud5, Dorssafe Fekiri3, Marie Robert3, Kim-Arthur Baffert3, Geneviève Hervé6, Pauline Quilhot6, Valéry Attignon3, Angélique Girod7, André Chaine7, Mourad Benassarou7, Philippe Zrounba8, Christophe Caux3, François Ghiringhelli9, Sylvie Lantuejoul10, Carole Crozes10, Isabelle Brochériou6, Maurice Pérol4, Jérôme Fayette4, Chloé Bertolus11, Pierre Saintigny12. 1. Sorbonne Université, Paris, France; Department of Maxillo-Facial Surgery, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France. Electronic address: jean-philippe.foy@aphp.fr. 2. Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France; Department of Medical Oncology, Centre Léon Bérard, 69008, Lyon, France. 3. Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France. 4. Department of Medical Oncology, Centre Léon Bérard, 69008, Lyon, France. 5. Sorbonne Université, Paris, France; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France. 6. Sorbonne Université, Paris, France; Department of Pathology, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France. 7. Sorbonne Université, Paris, France; Department of Maxillo-Facial Surgery, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France. 8. Department of Surgery, Centre Léon Bérard, 69008, Lyon, France. 9. Department of Medical Oncology, Centre Georges-François Leclerc, Dijon 21000, France. 10. Department of Pathology, Centre Léon Bérard, 69008, Lyon, France. 11. Sorbonne Université, Paris, France; Department of Maxillo-Facial Surgery, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France. 12. Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France; Department of Medical Oncology, Centre Léon Bérard, 69008, Lyon, France; Department of Translational Medicine, Centre Léon Bérard, 69008, Lyon, France. Electronic address: pierre.saintigny@lyon.unicancer.fr.
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.
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.