Predictors of responses to immune checkpoint blockade in advanced melanoma

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. 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 and L. Zitvogel ()
Additional contact information
N. Jacquelot: Gustave Roussy Cancer Campus
M. P. Roberti: Gustave Roussy Cancer Campus
D. P. Enot: Gustave Roussy Cancer Campus
S. Rusakiewicz: Gustave Roussy Cancer Campus
N. Ternès: University Paris-Saclay
S. Jegou: Saint Antoine Hospital
D. M. Woods: New York University Medical Center
A. L. Sodré: New York University Medical Center
M. Hansen: Copenhagen University Hospital
Y. Meirow: The Hebrew University Hadassah Medical School
M. Sade-Feldman: The Hebrew University Hadassah Medical School
A. Burra: University of California
S. S. Kwek: University of California
C. Flament: Gustave Roussy Cancer Campus
M. Messaoudene: Gustave Roussy Cancer Campus
C. P. M. Duong: Gustave Roussy Cancer Campus
L. Chen: Yale School of Medicine
B. S. Kwon: Eutilex
A. C. Anderson: Brigham and Women’s Hospital and Harvard Medical School
V. K. Kuchroo: Brigham and Women’s Hospital and Harvard Medical School
B. Weide: University Medical Center Tübingen
F. Aubin: Université de Franche Comté, EA3181, SFR4234, Service de Dermatologie, Centre Hospitalier Universitaire (CHU)
C. Borg: University Hospital of Besancon
S. Dalle: Hospices Civils de Lyon and University Claude Bernard Lyon 1
O. Beatrix: Hospices Civils de Lyon and University Claude Bernard Lyon 1
M. Ayyoub: Gustave Roussy Cancer Campus
B. Balme: Hospices Civils de Lyon and University Claude Bernard Lyon 1
G. Tomasic: Gustave Roussy Cancer Campus
A. M. Giacomo: University Hospital of Siena
M. Maio: University Hospital of Siena, Instituto Toscano Tumori
D. Schadendorf: University Hospital, University Duisburg-Essen, Essen, Germany & German Cancer Consortium (DKTZ)
I. Melero: Centre for Applied Medical Research
B. Dréno: CIC Biotherapy
A. Khammari: CIC Biotherapy
R. Dummer: University Hospital Zürich and University of Zürich
M. Levesque: University Hospital Zürich and University of Zürich
Y. Koguchi: Providence Cancer Center
L. Fong: University of California
M. Lotem: Hadassah Medical Organization
M. Baniyash: The Hebrew University Hadassah Medical School
H. Schmidt: Aarhus University Hospital
I. M. Svane: Copenhagen University Hospital
G. Kroemer: Gustave Roussy Cancer Campus
A. Marabelle: Gustave Roussy Cancer Campus
S. Michiels: Gustave Roussy Cancer Campus
A. Cavalcanti: Gustave Roussy Cancer Campus
M. J. Smyth: QIMR Berghofer Medical Research Institute
J. S. Weber: New York University Medical Center
A. M. Eggermont: Gustave Roussy Cancer Campus
L. Zitvogel: Gustave Roussy Cancer Campus

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00608-2

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