دورية أكاديمية
أعرض في EDS

Mature tertiary lymphoid structures are key niches of tumour-specific immune responses in pancreatic ductal adenocarcinomas.

التفاصيل البيبلوغرافية
العنوان: Mature tertiary lymphoid structures are key niches of tumour-specific immune responses in pancreatic ductal adenocarcinomas.
المؤلفون: Kinker GS; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Vitiello GAF; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Diniz AB; Hospital Israelita Albert Einstein, São Paulo, Brazil., Cabral-Piccin MP; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Pereira PHB; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Carvalho MLR; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Ferreira WAS; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil.; Evandro Chagas Institute, Ananindeua, Brazil., Chaves AS; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Rondinelli A; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Gusmão AF; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Defelicibus A; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil., Dos Santos GO; Department of Pathology, A.C.Camargo Cancer Center, São Paulo, Brazil., Nunes WA; Department of Pathology, A.C.Camargo Cancer Center, São Paulo, Brazil., Claro LCL; Faculty of Medical Sciences, Santa Casa de Misericórdia do Estado de São Paulo, São Paulo, Brazil., Bernardo TM; Faculty of Medical Sciences, Santa Casa de Misericórdia do Estado de São Paulo, São Paulo, Brazil., Nishio RT; Faculty of Medical Sciences, Santa Casa de Misericórdia do Estado de São Paulo, São Paulo, Brazil., Pacheco AM; Faculty of Medical Sciences, Santa Casa de Misericórdia do Estado de São Paulo, São Paulo, Brazil., Laus AC; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Arantes LMRB; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Fleck JL; Mines Saint-Etienne, Univ Clermont Auvergne, CNRS, UMR 6158 LIMOS, Centre CIS, Saint-Etienne, France., de Jesus VHF; Department of Medical Oncology, A.C.Camargo Cancer Center, São Paulo, Brazil., de Moricz A; Faculty of Medical Sciences, Santa Casa de Misericórdia do Estado de São Paulo, São Paulo, Brazil., Weinlich R; Hospital Israelita Albert Einstein, São Paulo, Brazil., Coimbra FJF; Department of Surgical Oncology, A.C.Camargo Cancer Center, São Paulo, Brazil., de Lima VCC; Department of Medical Oncology, A.C.Camargo Cancer Center, São Paulo, Brazil., Medina TDS; International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil tiago.medina@accamargo.org.br.; National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation, São Paulo, Brazil.
المصدر: Gut [Gut] 2023 Oct; Vol. 72 (10), pp. 1927-1941. Date of Electronic Publication: 2023 May 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: British Medical Assn Country of Publication: England NLM ID: 2985108R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-3288 (Electronic) Linking ISSN: 00175749 NLM ISO Abbreviation: Gut Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, British Medical Assn.
مواضيع طبية MeSH: Tertiary Lymphoid Structures*/metabolism , Tertiary Lymphoid Structures*/pathology , Pancreatic Neoplasms*/genetics , Carcinoma, Pancreatic Ductal*/genetics, Humans ; Immunity ; Tumor Microenvironment ; Pancreatic Neoplasms
مستخلص: Objective: To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for the generation of local antitumour immunity.
Design: We characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types. To evaluate the clinical relevance of our findings, we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial.
Results: We found that a subset of PDACs harbours fully developed TLSs where B cells proliferate and differentiate into plasma cells. These mature TLSs also support T cell activity and are enriched with tumour-reactive T cells. Importantly, we showed that chronically activated, tumour-reactive T cells exposed to fibroblast-derived TGF-β may act as TLS organisers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expanded CXCL13 + tumour-infiltrating T cells across multiple cancer types further indicated a conserved link between tumour-antigen recognition and the allocation of B cells within sheltered hubs in the tumour microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pretreatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens.
Conclusion: We provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.
Competing Interests: Competing interests: VCCL: honoraria (educational presentations and participation in scientific events) from Astra-Zeneca, MSD, BMS, Roche, Amgen, GSK, Lilly; advisory board from Astra-Zeneca, MSD, BMS, Pfizer, Janssen, Amgen.
(© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
فهرسة مساهمة: Keywords: IMMUNE RESPONSE; PANCREATIC CANCER
تواريخ الأحداث: Date Created: 20230525 Date Completed: 20230915 Latest Revision: 20231213
رمز التحديث: 20240628
DOI: 10.1136/gutjnl-2022-328697
PMID: 37230755
قاعدة البيانات: MEDLINE
الوصف
تدمد:1468-3288
DOI:10.1136/gutjnl-2022-328697