학술논문
Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma
Document Type
article
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
Source
Journal for ImmunoTherapy of Cancer, Vol 11, Iss 11 (2023)
Subject
Language
English
ISSN
2051-1426
Abstract
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