Predictors of responses to immune checkpoint blockade in advanced melanoma

被引：0

作者：

N. Jacquelot

M. P. Roberti

D. P. Enot

S. Rusakiewicz

N. Ternès

S. Jegou

D. M. Woods

A. L. Sodré

M. Hansen

Y. Meirow

M. Sade-Feldman

A. Burra

S. S. Kwek

C. Flament

M. Messaoudene

C. P. M. Duong

L. Chen

B. S. Kwon

A. C. Anderson

V. K. Kuchroo

B. Weide

F. Aubin

C. Borg

S. Dalle

O. Beatrix

M. Ayyoub

B. Balme

G. Tomasic

A. M. Di Giacomo

M. Maio

D. Schadendorf

I. Melero

B. Dréno

A. Khammari

R. Dummer

M. Levesque

Y. Koguchi

L. Fong

M. Lotem

M. Baniyash

H. Schmidt

I. M. Svane

G. Kroemer

A. Marabelle

S. Michiels

A. Cavalcanti

M. J. Smyth

J. S. Weber

A. M. Eggermont

L. Zitvogel

机构：

[1] Gustave Roussy Cancer Campus,INSERM U1015

[2] University Paris-Saclay,Metabolomics and Cell Biology Platforms

[3] Gustave Roussy Cancer Campus,CIC1428

[4] Gustave Roussy Cancer Campus,Gustave Roussy

[5] Gustave Roussy Cancer Campus,Laura & Isaac Perlmutter Cancer Center

[6] Université Paris-Saclay,Center for Cancer Immune Therapy, Department of Hematology and Oncology

[7] Service de Biostatistique et d’Epidémiologie,The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine

[8] Saint Antoine Hospital,Division of Hematology/Oncology, Department of Medicine

[9] New York University Medical Center,Department of Immunobiology

[10] Copenhagen University Hospital,Section of Clinical Immunology, Allergy, and Rheumatology, Department of Medicine

[11] The Hebrew University Hadassah Medical School,Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases

[12] University of California,Department of Dermatology

[13] Yale School of Medicine,Department of Medical Oncology

[14] Eutilex,Clinical Investigational Centre, CIC

[15] Tulane University Health Sciences Center,1431

[16] Brigham and Women’s Hospital and Harvard Medical School,INSERM U1098

[17] University Medical Center Tübingen,Centre Hospitalier Lyon

[18] Université de Franche Comté,Sud

[19] EA3181,Department of Pathology

[20] SFR4234,Department of Pathology

[21] Service de Dermatologie,Medical Oncology and Immunotherapy Division

[22] Centre Hospitalier Universitaire (CHU),Medical Oncology and Immunotherapy, Department of Oncology

[23] University Hospital of Besancon,Department of Dermatology

[24] University Hospital of Besançon,Division of Gene Therapy and Hepatology

[25] University of Franche-Comté,Oncology Department

[26] Hospices Civils de Lyon and University Claude Bernard Lyon 1,Department of Onco

[27] Centre de Recherche en Cancérologie de Lyon,dermatology

[28] Centre Hospitalier Lyon-Sud,Department of Dermatology

[29] Hospices Civils de Lyon,Earle A. Chiles Research Institute

[30] Gustave Roussy Cancer Campus,Sharett Institute of Oncology

[31] University Hospital of Siena,Department of Oncology

[32] University Hospital of Siena,INSERM U1138

[33] Instituto Toscano Tumori,Equipe 11 labellisée par la Ligue contre le Cancer

[34] University Hospital,Pôle de Biologie

[35] University Duisburg-Essen,Department of Surgery

[36] Essen,Department of Dermatology

[37] Germany & German Cancer Consortium (DKTZ),Immunology in Cancer and Infection Laboratory

[38] Centre for Applied Medical Research,School of Medicine

[39] University Clinic of Navarra,undefined

[40] Centro de Investigación cBiomedica en Red de Oncologia,undefined

[41] CIC Biotherapy,undefined

[42] University Hospital Zürich and University of Zürich,undefined

[43] Providence Cancer Center,undefined

[44] Hadassah Medical Organization,undefined

[45] Aarhus University Hospital,undefined

[46] Centre de Recherche des Cordeliers,undefined

[47] Centre de Recherche des Cordeliers,undefined

[48] Université Paris Descartes,undefined

[49] Université Pierre et Marie Curie,undefined

[50] Hôpital Européen Georges Pompidou,undefined

来源：

Nature Communications | / 8卷

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摘要：

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.

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