High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas
| Autor: | M-T Chaumette, François Berrehar, Antoine Charachon, Mehdi Karoui, S. Bastuji-Garin, J-P Farcet, S. Le Gouvello, Iradj Sobhani, A Seikour, Karen Leroy, Hicham Mansour, Nijez Aloulou |
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| Přispěvatelé: | Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Département de pathologie [Mondor], Service de chirurgie digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Supported by grants from DRCD Assistance Publique – Hôpitaux de Paris, Ligue contre le cancer, ACD., Guellaen, Georges |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Pathology medicine.medical_specialty CD3 Complex Colorectal cancer Colon DNA Mismatch Repair 03 medical and health sciences 0302 clinical medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology medicine Biomarkers Tumor Cytotoxic T cell Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Intestinal Mucosa Immunity Mucosal MSI 030304 developmental biology Aged Neoplasm Staging Retrospective Studies 0303 health sciences IL-6 biology business.industry Reverse Transcriptase Polymerase Chain Reaction Interleukin-17 Gastroenterology FOXP3 Microsatellite instability Cancer Forkhead Transcription Factors medicine.disease digestive system diseases 3. Good health Granzyme B IL-17 Phenotype Perforin colon cancer 030220 oncology & carcinogenesis Foxp3 biology.protein Cancer research Immunohistochemistry Female business Colorectal Neoplasms |
| Zdroj: | Gut Gut, BMJ Publishing Group, 2008, 57 (6), pp.772-9. ⟨10.1136/gut.2007.123794⟩ |
| ISSN: | 0017-5749 1468-3288 |
| Popis: | International audience; BACKGROUND AND AIMS: Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour immune response in mismatch repair (MMR)-proficient (MSS) colon cancers. METHODS: Ninety human colon cancers (T) and autologous normal colon mucosa (NT) were quantified for the expression of 15 markers of the immune response with quantitiative reverse transcription-PCR (qRT-PCR). mRNA expression levels were correlated with MMR status. Immunohistochemistry (IHC) was performed using both interleukin 17 (IL17) and CD3 antibodies. RESULTS: Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL1beta, IL6, IL8, IL17 and transforming growth factor beta (TGFbeta)) and a marker of regulatory T cells (forkhead box P3 (Foxp3)) was significantly higher in tumours than in autologous normal tissues. Adjusting for MMR status, higher tumoural expression of both granzyme B and perforin was associated with the MSI-H phenotype, and the perforin T/NT ratio was higher in MSI-H tissues than in MSS tissues. Higher tumoural expression of Foxp3, IL17, IL1beta, IL6 and TGFbeta was associated with the MSS phenotype, and the IL17 T/NT ratio was higher in MSS tissues than in MSI-H tissues as assessed by both qRT-PCR and IHC. CONCLUSIONS: Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL6, TGFbeta and IL17 expression is a particular determinant in MMR-proficient CRC. These may be potential biomarkers for a new prognostic "test set" in sporadic CRCs. |
| Databáze: | OpenAIRE |
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