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. 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

doi:10.1038/s41467-017-00608-2

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. KuchrooB. 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

Department of Immunology and Cancer Research

The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	592
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00608-2
State	Published - 1 Dec 2017

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-017-00608-2

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Jacquelot, N., Roberti, M. P., Enot, D. P., Rusakiewicz, S., Ternès, N., Jegou, S., Woods, D. M., Sodré, A. L., Hansen, M., Meirow, Y., Sade-Feldman, M., Burra, A., Kwek, S. S., Flament, C., Messaoudene, M., Duong, C. P. M., Chen, L., Kwon, B. S., Anderson, A. C., ... Zitvogel, L. (2017). Predictors of responses to immune checkpoint blockade in advanced melanoma. Nature Communications, 8(1), Article 592. https://doi.org/10.1038/s41467-017-00608-2

@article{4063bd5c653943aba39fbea5d65b9347,

title = "Predictors of responses to immune checkpoint blockade in advanced melanoma",

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.",

author = "N. Jacquelot and Roberti, \{M. P.\} and Enot, \{D. P.\} and S. Rusakiewicz and N. Tern{\`e}s and S. Jegou and Woods, \{D. M.\} and Sodr{\'e}, \{A. L.\} and M. Hansen and Y. Meirow and M. Sade-Feldman and A. Burra and Kwek, \{S. S.\} and C. Flament and M. Messaoudene and Duong, \{C. P.M.\} and L. Chen and Kwon, \{B. S.\} and Anderson, \{A. C.\} and Kuchroo, \{V. K.\} and B. Weide and F. Aubin and C. Borg and S. Dalle and O. Beatrix and M. Ayyoub and B. Balme and G. Tomasic and \{Di Giacomo\}, \{A. M.\} and M. Maio and D. Schadendorf and I. Melero and B. Dr{\'e}no and A. Khammari and R. Dummer and M. Levesque and Y. Koguchi and L. Fong and M. Lotem and M. Baniyash and H. Schmidt and Svane, \{I. M.\} and G. Kroemer and A. Marabelle and S. Michiels and A. Cavalcanti and Smyth, \{M. J.\} and Weber, \{J. S.\} and Eggermont, \{A. M.\} and L. Zitvogel",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-00608-2",

language = "الإنجليزيّة",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Jacquelot, N, Roberti, MP, Enot, DP, Rusakiewicz, S, Ternès, N, Jegou, S, Woods, DM, Sodré, AL, Hansen, M, Meirow, Y, Sade-Feldman, M, Burra, A, Kwek, SS, Flament, C, Messaoudene, M, Duong, CPM, Chen, L, Kwon, BS, Anderson, AC, Kuchroo, VK, Weide, B, Aubin, F, Borg, C, Dalle, S, Beatrix, O, Ayyoub, M, Balme, B, Tomasic, G, Di Giacomo, AM, Maio, M, Schadendorf, D, Melero, I, Dréno, B, Khammari, A, Dummer, R, Levesque, M, Koguchi, Y, Fong, L, Lotem, M, Baniyash, M, Schmidt, H, Svane, IM, Kroemer, G, Marabelle, A, Michiels, S, Cavalcanti, A, Smyth, MJ, Weber, JS, Eggermont, AM & Zitvogel, L 2017, 'Predictors of responses to immune checkpoint blockade in advanced melanoma', Nature Communications, vol. 8, no. 1, 592. https://doi.org/10.1038/s41467-017-00608-2

TY - JOUR

T1 - Predictors of responses to immune checkpoint blockade in advanced melanoma

AU - Jacquelot, N.

AU - Roberti, M. P.

AU - Enot, D. P.

AU - Rusakiewicz, S.

AU - Ternès, N.

AU - Jegou, S.

AU - Woods, D. M.

AU - Sodré, A. L.

AU - Hansen, M.

AU - Meirow, Y.

AU - Sade-Feldman, M.

AU - Burra, A.

AU - Kwek, S. S.

AU - Flament, C.

AU - Messaoudene, M.

AU - Duong, C. P.M.

AU - Chen, L.

AU - Kwon, B. S.

AU - Anderson, A. C.

AU - Kuchroo, V. K.

AU - Weide, B.

AU - Aubin, F.

AU - Borg, C.

AU - Dalle, S.

AU - Beatrix, O.

AU - Ayyoub, M.

AU - Balme, B.

AU - Tomasic, G.

AU - Di Giacomo, A. M.

AU - Maio, M.

AU - Schadendorf, D.

AU - Melero, I.

AU - Dréno, B.

AU - Khammari, A.

AU - Dummer, R.

AU - Levesque, M.

AU - Koguchi, Y.

AU - Fong, L.

AU - Lotem, M.

AU - Baniyash, M.

AU - Schmidt, H.

AU - Svane, I. M.

AU - Kroemer, G.

AU - Marabelle, A.

AU - Michiels, S.

AU - Cavalcanti, A.

AU - Smyth, M. J.

AU - Weber, J. S.

AU - Eggermont, A. M.

AU - Zitvogel, L.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85029870193&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-00608-2

DO - 10.1038/s41467-017-00608-2

M3 - مقالة

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 592

ER -

Predictors of responses to immune checkpoint blockade in advanced melanoma

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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