Intrahepatic CD69


Journal

Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585

Informations de publication

Date de publication:
07 2022
Historique:
accepted: 01 07 2022
entrez: 21 7 2022
pubmed: 22 7 2022
medline: 26 7 2022
Statut: ppublish

Résumé

More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack of reliable prognostic markers. Vδ1 cells are a subset of tissue-resident gamma delta (γδ) T lymphocytes endowed with a broad array of antitumor functions and showing a natural high tropism for the liver. However, little is known about their impact in the clinical outcomes of CLM. We isolated human γδ T cells from peripheral blood (PB) and peritumoral (PT) tissue of 93 patients undergone surgical procedures to remove CLM. The phenotype of freshly purified γδ T cells was assessed by multiparametric flow cytometry, the transcriptional profiles by single cell RNA-sequencing, the functional annotations by Gene Ontology enrichment analyses and the clonotype by γδ T cell receptor (TCR)-sequencing. The microenvironment of CLM is characterized by a heterogeneous immune infiltrate comprising different subsets of γδ tumor-infiltrating lymphocytes (TILs) able to egress the liver and re-circulate in PB. Vδ1 T cells represent the largest population of γδ TILs within the PT compartment of CLM that is greatly enriched in Vδ1 T effector (T The enrichment of tissue-resident CD69

Sections du résumé

BACKGROUND
More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack of reliable prognostic markers. Vδ1 cells are a subset of tissue-resident gamma delta (γδ) T lymphocytes endowed with a broad array of antitumor functions and showing a natural high tropism for the liver. However, little is known about their impact in the clinical outcomes of CLM.
METHODS
We isolated human γδ T cells from peripheral blood (PB) and peritumoral (PT) tissue of 93 patients undergone surgical procedures to remove CLM. The phenotype of freshly purified γδ T cells was assessed by multiparametric flow cytometry, the transcriptional profiles by single cell RNA-sequencing, the functional annotations by Gene Ontology enrichment analyses and the clonotype by γδ T cell receptor (TCR)-sequencing.
RESULTS
The microenvironment of CLM is characterized by a heterogeneous immune infiltrate comprising different subsets of γδ tumor-infiltrating lymphocytes (TILs) able to egress the liver and re-circulate in PB. Vδ1 T cells represent the largest population of γδ TILs within the PT compartment of CLM that is greatly enriched in Vδ1 T effector (T
CONCLUSIONS
The enrichment of tissue-resident CD69

Identifiants

pubmed: 35863820
pii: jitc-2022-004579
doi: 10.1136/jitc-2022-004579
pmc: PMC9310256
pii:
doi:

Substances chimiques

Receptors, Antigen, T-Cell, gamma-delta 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Elena Bruni (E)

Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.

Matteo Maria Cimino (MM)

Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Matteo Donadon (M)

Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Health Science, Università del Piemonte Orientale, Novara, Italy.

Roberta Carriero (R)

Bioinformatics Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Sara Terzoli (S)

Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Rocco Piazza (R)

Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.

Sarina Ravens (S)

Institute of Immunology, Hannover Medical School (MHH), Hannover, Germany.

Immo Prinz (I)

Institute of Immunology, Hannover Medical School (MHH), Hannover, Germany.
Institute of Systems Immunology, Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Valentina Cazzetta (V)

Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.

Paolo Marzano (P)

Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.

Paolo Kunderfranco (P)

Bioinformatics Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Clelia Peano (C)

Institute of Biomedical Technologie, CNR Milan, Human Technopole, Milan, Italy.

Cristiana Soldani (C)

Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Barbara Franceschini (B)

Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Federico Simone Colombo (FS)

Humanitas Flow Cytometry Core, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Cecilia Garlanda (C)

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Alberto Mantovani (A)

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
The William Harvey Research Institute, Queen Mary University of London, London, UK.

Guido Torzilli (G)

Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Joanna Mikulak (J)

Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.

Domenico Mavilio (D)

Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy domenico.mavilio@humanitas.it.
Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.

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