dataset
posted on 2023-03-31, 19:29 authored by Etienne Becht, Aurélien de Reyniès, Nicolas A. Giraldo, Camilla Pilati, Bénédicte Buttard, Laetitia Lacroix, Janick Selves, Catherine Sautès-Fridman, Pierre Laurent-Puig, Wolf Herman Fridman Levels of expression of genes related to inflammation, angiogenesis and immunomodulation in CRC cohorts
Funding
Institut National de la Santé et de la Recherche Médicale
University Pierre et Marie Curie
Institut National Du Cancer
CARPEM, Labex Immuno-Oncology
Fondation ARC pour la Recherche sur le Cancer
Cancérop⊚le Ile-de-France
Universidad de los Andes
Colciencias
B3MI doctorate
PPATH doctorate
History
ARTICLE ABSTRACT
Purpose: The tumor microenvironment is formed by many distinct and interacting cell populations, and its composition may predict patients' prognosis and response to therapies. Colorectal cancer is a heterogeneous disease in which immune classifications and four consensus molecular subgroups (CMS) have been described. Our aim was to integrate the composition of the tumor microenvironment with the consensus molecular classification of colorectal cancer.Experimental Design: We retrospectively analyzed the composition and the functional orientation of the immune, fibroblastic, and angiogenic microenvironment of 1,388 colorectal cancer tumors from three independent cohorts using transcriptomics. We validated our findings using immunohistochemistry.Results: We report that colorectal cancer molecular subgroups and microenvironmental signatures are highly correlated. Out of the four molecular subgroups, two highly express immune-specific genes. The good-prognosis microsatellite instable–enriched subgroup (CMS1) is characterized by overexpression of genes specific to cytotoxic lymphocytes. In contrast, the poor-prognosis mesenchymal subgroup (CMS4) expresses markers of lymphocytes and of cells of monocytic origin. The mesenchymal subgroup also displays an angiogenic, inflammatory, and immunosuppressive signature, a coordinated pattern that we also found in breast (n = 254), ovarian (n = 97), lung (n = 80), and kidney (n = 143) cancers. Pathologic examination revealed that the mesenchymal subtype is characterized by a high density of fibroblasts that likely produce the chemokines and cytokines that favor tumor-associated inflammation and support angiogenesis, resulting in a poor prognosis. In contrast, the canonical (CMS2) and metabolic (CMS3) subtypes with intermediate prognosis exhibit low immune and inflammatory signatures.Conclusions: The distinct immune orientations of the colorectal cancer molecular subtypes pave the way for tailored immunotherapies. Clin Cancer Res; 22(16); 4057–66. ©2016 AACR.
