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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

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    1 Equally contributed to this work.
    ,
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    2 Co-corresponding authors
    Jean-Philippe Foy
    Correspondence
    Corresponding author: Sorbonne Université, Department of Maxillo-Facial Surgery, Hôpital Pitié-Salpêtrière, 47-83 boulevard de l’Hôpital, 75013 Paris France. Fax: +33-(0)142161449.
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    1 Equally contributed to this work.
    2 Co-corresponding authors
    Affiliations
    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
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    1 Equally contributed to this work.
    Andy Karabajakian
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    1 Equally contributed to this work.
    Affiliations
    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
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  • Author Footnotes
    1 Equally contributed to this work.
    Sandra Ortiz-Cuaran
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    1 Equally contributed to this work.
    Affiliations
    Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
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    Maxime Boussageon
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    1 Equally contributed to this work.
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    Department of Medical Oncology, Centre Léon Bérard, 69008, Lyon, France
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  • Lucas Michon
    Affiliations
    Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
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  • Jebrane Bouaoud
    Affiliations
    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
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  • Dorssafe Fekiri
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    Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
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  • Marie Robert
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    Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
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  • Kim-Arthur Baffert
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    Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
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  • Geneviève Hervé
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    Sorbonne Université, Paris, France

    Department of Pathology, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France
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  • Pauline Quilhot
    Affiliations
    Sorbonne Université, Paris, France

    Department of Pathology, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France
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  • Valéry Attignon
    Affiliations
    Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
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  • Angélique Girod
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    Sorbonne Université, Paris, France

    Department of Maxillo-Facial Surgery, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France
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  • André Chaine
    Affiliations
    Sorbonne Université, Paris, France

    Department of Maxillo-Facial Surgery, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France
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  • Mourad Benassarou
    Affiliations
    Sorbonne Université, Paris, France

    Department of Maxillo-Facial Surgery, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France
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  • Philippe Zrounba
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    Department of Surgery, Centre Léon Bérard, 69008, Lyon, France
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  • Christophe Caux
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    Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
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  • François Ghiringhelli
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    Department of Medical Oncology, Centre Georges-François Leclerc, Dijon 21000, France
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  • Sylvie Lantuejoul
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    Department of Pathology, Centre Léon Bérard, 69008, Lyon, France
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  • Carole Crozes
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    Department of Pathology, Centre Léon Bérard, 69008, Lyon, France
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  • Isabelle Brochériou
    Affiliations
    Sorbonne Université, Paris, France

    Department of Pathology, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France
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  • Maurice Pérol
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    Department of Medical Oncology, Centre Léon Bérard, 69008, Lyon, France
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  • Jérôme Fayette
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    Department of Medical Oncology, Centre Léon Bérard, 69008, Lyon, France
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  • Chloé Bertolus
    Affiliations
    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
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  • Author Footnotes
    2 Co-corresponding authors
    Pierre Saintigny
    Correspondence
    Corresponding author: Department of Medical Oncology, Centre Léon Bérard; 28 rue Laennec, 69373 Lyon Cedex 08, France. Fax: +33-(0)478782868.
    Footnotes
    2 Co-corresponding authors
    Affiliations
    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
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  • Author Footnotes
    1 Equally contributed to this work.
    2 Co-corresponding authors
Published:August 26, 2022DOI:https://doi.org/10.1016/j.ejca.2022.06.034

      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.

      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.

      Keywords

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