Prevalence and Cellular Distribution of Novel Immune Checkpoint Targets Across Longitudinal Specimens in Treatment-naïve Melanoma Patients: Implications for Clinical Trials.

Antineoplastic Agents, Immunological / pharmacology Biomarkers, Tumor Biopsy Humans Immunohistochemistry Immunomodulation / drug effects Immunophenotyping Leukocytes / drug effects Longitudinal Studies Melanoma / diagnosis T-Lymphocytes / drug effects

Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
01 06 2019
Historique:
received: 10 12 2018
revised: 18 01 2019
accepted: 13 02 2019
pubmed: 20 2 2019
medline: 7 7 2020
entrez: 20 2 2019
Statut: ppublish

Résumé

Immunotherapies targeting costimulating and coinhibitory checkpoint receptors beyond PD-1 and CTLA-4 have entered clinical trials. Little is known about the relative abundance, coexpression, and immune cells enriched for each specific drug target, limiting understanding of the biological basis of potential treatment outcomes and development of predictive biomarkers for personalized immunotherapy. We sought to assess the abundance of checkpoint receptors during melanoma disease progression and identify immune cells enriched for them. A small subset of tumor-infiltrating leukocytes expressed checkpoint receptors at any stage of melanoma disease. GITR and OX40 were the least abundant checkpoint receptors, with <1% of intratumoral T cells expressing either marker. ICOS, PD-1, TIM-3, and VISTA were most abundant, with TIM-3 and VISTA mostly expressed on non-T cells, and TIM-3 enriched on dendritic cells. Tumor-resident T cells (CD69 This study provides the first comprehensive assessment of immune checkpoint receptor expression in any cancer and provides important data for rational selection of targets for trials and predictive biomarker development.

Identifiants

DOI: 10.1158/1078-0432.CCR-18-4011 PMID: 30777877
pubmed: 30777877
pii: 1078-0432.CCR-18-4011
doi: 10.1158/1078-0432.CCR-18-4011
doi:

Substances chimiques

Antineoplastic Agents, Immunological 0
Biomarkers, Tumor 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

3247-3258

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

©2019 American Association for Cancer Research.

Auteurs

Jarem Edwards (J)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

Annie Tasker (A)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

Inês Pires da Silva (I)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.

Camelia Quek (C)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

Marcel Batten (M)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

Angela Ferguson (A)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

Ruth Allen (R)

Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.

Benjamin Allanson (B)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

Robyn P M Saw (RPM)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Mater Hospital, North Sydney, Australia.

John F Thompson (JF)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Mater Hospital, North Sydney, Australia.
ORCID: 0000-0002-2816-2496

Alexander M Menzies (AM)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Mater Hospital, North Sydney, Australia.
Royal North Shore Hospital, Sydney, New South Wales Australia.

Umaimainthan Palendira (U)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

James S Wilmott (JS)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
ORCID: 0000-0002-6750-5244

Georgina V Long (GV)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
Mater Hospital, North Sydney, Australia.
Royal North Shore Hospital, Sydney, New South Wales Australia.

Richard A Scolyer (RA)

Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia. Richard.Scolyer@melanoma.org.au.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
ORCID: 0000-0002-8991-0013

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytodiagnostic › Biopsie › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Immunohistochimie › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunomodulation › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Tests immunologiques › Immunophénotypage › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études longitudinales › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Prevalence and Cellular Distribution of Novel...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Prevalence and Cellular Distribution of Novel...