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 Clinical Medicine

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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
Number of pages	13
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-017-00608-2
Publication status	Published - 1 Dec 2017

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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, [592]. https://doi.org/10.1038/s41467-017-00608-2

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, 592. https://doi.org/10.1038/s41467-017-00608-2

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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.",

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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.

KW - Journal Article

U2 - 10.1038/s41467-017-00608-2

DO - 10.1038/s41467-017-00608-2

M3 - Journal article

C2 - 28928380

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 592

ER -

Predictors of responses to immune checkpoint blockade in advanced melanoma

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