1. Revisiting immune escape in colorectal cancer in the era of immunotherapy
- Author
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Hans Morreau, Marieke E. Ijsselsteijn, Catherine Sautès-Fridman, Florent Petitprez, Noel Filipe da Cunha Carvalho de Miranda, Ruud van der Breggen, Laetitia Lacroix, Catherine Julie, Wolf H. Fridman, Dina Ruano, Leiden University Medical Center (LUMC), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Sorbonne Paris Cité (USPC), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP]
- Subjects
Male ,Cancer Research ,Carcinogenesis ,Colorectal cancer ,T-Lymphocytes ,medicine.medical_treatment ,Antigen presentation ,Genes, MHC Class I ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Human leukocyte antigen ,Brief Communication ,medicine.disease_cause ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Immunoediting ,Neoplastic Syndromes, Hereditary ,medicine ,Humans ,Neoplasm Metastasis ,Oncogenesis ,Regulation of gene expression ,Antigen Presentation ,Brain Neoplasms ,Immune evasion ,business.industry ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,Immunotherapy ,Middle Aged ,medicine.disease ,Phenotype ,digestive system diseases ,3. Good health ,Blockade ,Gene Expression Regulation, Neoplastic ,Genes, cdc ,Liver ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Colorectal Neoplasms ,business - Abstract
International audience; In colorectal cancer (CRC), T-cell checkpoint blockade is only effective in patients diagnosed with mismatch repair-deficient (MMR-d) cancers. However, defects in Human Leukocyte Antigen (HLA) class I expression were reported to occur in most MMR-d CRCs, which would preclude antigen presentation in these tumours, considered essential for the clinical activity of this immunotherapeutic modality. We revisited this paradox by characterising HLA class I expression in two independent cohorts of CRC. We determined that loss of HLA class I expression occurred in the majority (73-78%) of MMR-d cases. This phenotype was rare in CRC liver metastases, irrespective of MMR status, whereas weak, inducible expression of HLA class I molecules was frequent in liver lesions. We propose that HLA class I is an important determinant of metastatic homing in CRCs. This observation is paramount to understand CRC carcinogenesis and for the application of immunotherapies in the metastatic setting.
- Published
- 2019