Juliette Paillet1,2,3,4,5,6, Guido Kroemer1,2,3,4,5,7,8,9, Jonathan G Pol1,2,3,4,5. 1. Institut National de la Santé et de la Recherche Médicale (INSERM), U1138. 2. Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers. 3. Sorbonne Université. 4. Université de Paris. 5. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus. 6. Université Paris-Sud/Paris XI, Faculté de Médecine. 7. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. 8. Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, China. 9. Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
Abstract
PURPOSE OF REVIEW: Considering the failure of standard treatments (i.e. surgery, radiotherapy, chemotherapy) in treating cholangiocarcinoma (CCA), introduction of alternative interventions is urgently needed. During the past 2 decades, discoveries of the mechanisms of cancer immunosurveillance and tumor immune evasion have precipitated the emergence and clinical approval of immunotherapies in multiple malignant indications. Interest in their introduction for the care of CCA is recent and several immunotherapeutic approaches are undergoing a clinical evaluation. Undoubtedly, their efficient application, as monotherapy or in combination regimens, will rely on a deeper understanding of CCA immune contexture. RECENT FINDINGS: CCA cells appeared very potent in recruiting protumorigenic cells and shaping an immunosuppressive microenvironment. Elevated densities of several immune cells with immunoinhibitory activities within the malignant bed have been associated with poor prognosis in patients. Particularly, macrophages and neutrophils (especially in their alternatively activated phenotype) were pointed out for their role in cancer progression. Dendritic cells were described as ineffective in priming CCA-specific T-cell responses. SUMMARY: Quantitative and qualitative assessment of the innate and adaptive immune compartments of the CCA immune contexture, as well as their prognostic value, will benefit to the development of improved immunotherapeutic strategies.
PURPOSE OF REVIEW: Considering the failure of standard treatments (i.e. surgery, radiotherapy, chemotherapy) in treating cholangiocarcinoma (CCA), introduction of alternative interventions is urgently needed. During the past 2 decades, discoveries of the mechanisms of cancer immunosurveillance and tumor immune evasion have precipitated the emergence and clinical approval of immunotherapies in multiple malignant indications. Interest in their introduction for the care of CCA is recent and several immunotherapeutic approaches are undergoing a clinical evaluation. Undoubtedly, their efficient application, as monotherapy or in combination regimens, will rely on a deeper understanding of CCA immune contexture. RECENT FINDINGS:CCA cells appeared very potent in recruiting protumorigenic cells and shaping an immunosuppressive microenvironment. Elevated densities of several immune cells with immunoinhibitory activities within the malignant bed have been associated with poor prognosis in patients. Particularly, macrophages and neutrophils (especially in their alternatively activated phenotype) were pointed out for their role in cancer progression. Dendritic cells were described as ineffective in priming CCA-specific T-cell responses. SUMMARY: Quantitative and qualitative assessment of the innate and adaptive immune compartments of the CCA immune contexture, as well as their prognostic value, will benefit to the development of improved immunotherapeutic strategies.
Authors: Juliette Paillet; Céleste Plantureux; Sarah Lévesque; Julie Le Naour; Gautier Stoll; Allan Sauvat; Pamela Caudana; Jimena Tosello Boari; Norma Bloy; Sylvie Lachkar; Isabelle Martins; Paule Opolon; Andrea Checcoli; Agathe Delaune; Noémie Robil; Pierre de la Grange; Juliette Hamroune; Franck Letourneur; Gwennhael Autret; Patrick S C Leung; M Eric Gershwin; Jie S Zhu; Mark J Kurth; Bouchra Lekbaby; Jérémy Augustin; Youra Kim; Shashi Gujar; Cédric Coulouarn; Laura Fouassier; Laurence Zitvogel; Eliane Piaggio; Chantal Housset; Patrick Soussan; Maria Chiara Maiuri; Guido Kroemer; Jonathan G Pol Journal: J Exp Med Date: 2021-09-08 Impact factor: 14.307