Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma
Background Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and iden...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-11-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/11/e006885.full |
| _version_ | 1797426891723898880 |
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| author | Laurence Albiges Bernard Escudier Gwenaelle Gravis Ronan Flippot Alain Ravaud Maxime Meylan Nathalie Rioux-Leclercq Marine Gross-Goupil Gaëlle Fromont Christophe Passot Lionnel Geoffrois Fréderic Rolland Manon de Vries-Brilland Jonathan Dauvé Elena Spirina-Menand Christine Chevreau Ellen Blanc Félix Lefort Sylvie Negrier |
| author_facet | Laurence Albiges Bernard Escudier Gwenaelle Gravis Ronan Flippot Alain Ravaud Maxime Meylan Nathalie Rioux-Leclercq Marine Gross-Goupil Gaëlle Fromont Christophe Passot Lionnel Geoffrois Fréderic Rolland Manon de Vries-Brilland Jonathan Dauvé Elena Spirina-Menand Christine Chevreau Ellen Blanc Félix Lefort Sylvie Negrier |
| author_sort | Laurence Albiges |
| collection | DOAJ |
| description | Background Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets.Methods We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort.Results Unsupervised clustering identified two “TME subtypes”, in each of the cohorts: the “immune-enriched” and the “immune-low”. Within AXIPAP trial cohort, the “immune-enriched” cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the “immune-enriched” group (adjusted p<0.05). Finally, five differentially overexpressed genes were identified, corresponding mainly to B lymphocyte populations.Conclusion For the first time, using RNA-seq and immunohistochemistry, we have highlighted a specific immune TME subtype of metastatic pRCC, significantly more infiltrated with T and B immune population. This “immune-enriched” group appears to have a worse prognosis and could have a potential predictive value for response to immunotherapy, justifying the confirmation of these results in a cohort of metastatic pRCC treated with CPI and in combination with targeted therapies.Trial registration number NCT02489695. |
| first_indexed | 2024-03-09T08:37:21Z |
| format | Article |
| id | doaj.art-e2ce2468aad14a5187730a92accb65ce |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-03-09T08:37:21Z |
| publishDate | 2023-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-e2ce2468aad14a5187730a92accb65ce2023-12-02T18:10:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-11-01111110.1136/jitc-2023-006885Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinomaLaurence Albiges0Bernard Escudier1Gwenaelle Gravis2Ronan Flippot3Alain Ravaud4Maxime Meylan5Nathalie Rioux-Leclercq6Marine Gross-Goupil7Gaëlle Fromont8Christophe Passot9Lionnel Geoffrois10Fréderic Rolland11Manon de Vries-Brilland12Jonathan Dauvé13Elena Spirina-Menand14Christine Chevreau15Ellen Blanc16Félix Lefort17Sylvie Negrier18Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, FranceMedical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, FranceMedical Oncology, Institut Paoli-Calmettes, Marseille, FranceMedical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, FranceDepartment of Medical Oncology, University Hospital of Bordeaux, Bordeaux, FranceEquipe inflammation, complément et cancer, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris-Cité, Paris, FranceDepartment of Pathology, University Hospital, Rennes, FranceDepartment of Medical Oncology, University Hospital of Bordeaux, Bordeaux, FranceDepartment of Pathology, CHRU, Tours, FranceDepartment of Clinical Biology, Integrated Centers of Oncology (ICO) Paul Papin, Angers, FranceDepartment of Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, FranceDepartment of Medical Oncology, Integrated Centers of Oncology (ICO) René Gauducheau, Nantes, FranceDepartment of Medical Oncology, Integrated Centers of Oncology (ICO) Paul Papin, Angers, FranceDepartment of Clinical Biology, Integrated Centers of Oncology (ICO) Paul Papin, Angers, FranceDepartment of Clinical Biology, Integrated Centers of Oncology (ICO) Paul Papin, Angers, FranceDepartment of Medical Oncology, IUCT-Oncopôle Institut Claudius Regaud, Toulouse, FranceDepartment of Clinical Research and Innovation, Centre Léon Bérard, Lyon, FranceDepartment of Medical Oncology, University Hospital of Bordeaux, Bordeaux, FranceDepartment of Medical Oncology, Lyon I University, Lyon, FranceBackground Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets.Methods We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort.Results Unsupervised clustering identified two “TME subtypes”, in each of the cohorts: the “immune-enriched” and the “immune-low”. Within AXIPAP trial cohort, the “immune-enriched” cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the “immune-enriched” group (adjusted p<0.05). Finally, five differentially overexpressed genes were identified, corresponding mainly to B lymphocyte populations.Conclusion For the first time, using RNA-seq and immunohistochemistry, we have highlighted a specific immune TME subtype of metastatic pRCC, significantly more infiltrated with T and B immune population. This “immune-enriched” group appears to have a worse prognosis and could have a potential predictive value for response to immunotherapy, justifying the confirmation of these results in a cohort of metastatic pRCC treated with CPI and in combination with targeted therapies.Trial registration number NCT02489695.https://jitc.bmj.com/content/11/11/e006885.full |
| spellingShingle | Laurence Albiges Bernard Escudier Gwenaelle Gravis Ronan Flippot Alain Ravaud Maxime Meylan Nathalie Rioux-Leclercq Marine Gross-Goupil Gaëlle Fromont Christophe Passot Lionnel Geoffrois Fréderic Rolland Manon de Vries-Brilland Jonathan Dauvé Elena Spirina-Menand Christine Chevreau Ellen Blanc Félix Lefort Sylvie Negrier Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma Journal for ImmunoTherapy of Cancer |
| title | Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma |
| title_full | Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma |
| title_fullStr | Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma |
| title_full_unstemmed | Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma |
| title_short | Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma |
| title_sort | comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma |
| url | https://jitc.bmj.com/content/11/11/e006885.full |
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