Predictors of responses to immune checkpoint blockade in advanced melanoma

被引：165

作者：

Jacquelot, N. ^{[1
,2
,3
]}

Roberti, M. P. ^{[1
,3
]}

Enot, D. P. ^{[3
,4
]}

Rusakiewicz, S. ^{[1
,3
,5
]}

Ternes, N. ^{[2
,3
,6
]}

Jegou, S. ^{[7
]}

Woods, D. M. ^{[8
]}

Sodre, A. L. ^{[8
]}

Hansen, M. ^{[9
]}

Meirow, Y. ^{[10
]}

Sade-Feldman, M. ^{[10
]}

Burra, A. ^{[11
]}

Kwek, S. S. ^{[11
]}

Flament, C. ^{[1
,2
,3
,5
]}

Messaoudene, M. ^{[1
,3
]}

Duong, C. P. M. ^{[1
,3
]}

Chen, L. ^{[12
]}

Kwon, B. S. ^{[13
,14
]}

Anderson, A. C. ^{[15
,16
,17
]}

Kuchroo, V. K. ^{[15
,16
,17
]}

Weide, B. ^{[18
]}

Aubin, F. ^{[19
]}

Borg, C. ^{[20
,21
,22
]}

Dalle, S. ^{[23
,24
,25
]}

Beatrix, O. ^{[23
,24
]}

Ayyoub, M. ^{[1
,3
]}

Balme, B. ^{[23
,24
,26
]}

Tomasic, G. ^{[3
,27
]}

Di Giacomo, A. M. ^{[28
]}

Maio, M. ^{[29
]}

Schadendorf, D. ^{[30
,31
]}

Melero, I. ^{[32
,33
,34
]}

Dreno, B. ^{[35
]}

Khammari, A. ^{[35
]}

Dummer, R. ^{[36
,37
]}

Levesque, M. ^{[36
,37
]}

Koguchi, Y. ^{[38
]}

Fong, L. ^{[11
]}

Lotem, M. ^{[39
]}

Baniyash, M. ^{[10
]}

Schmidt, H. ^{[40
]}

Svane, I. M. ^{[9
]}

Kroemer, G. ^{[3
,4
,41
,42
,43
,44
,45
]}

Marabelle, A. ^{[1
,3
,5
]}

Michiels, S. ^{[3
,6
]}

Cavalcanti, A. ^{[3
,46
,47
]}

Smyth, M. J. ^{[48
,49
]}

Weber, S. ^{[8
]}

Eggermont, A. M. ^{[3
]}

Zitvogel, L. ^{[1
,2
,3
,5
,6
]}

机构：

[1] INSERM, U1015, Gustave Roussy Canc Campus, F-94800 Villejuif, France

[2] Univ Paris Saclay, F-94276 Le Kremlin Bicetre, France

[3] Gustave Roussy Canc Campus, F-94800 Villejuif, France

[4] Metabolom & Cell Biol Platforms, Gustave Roussy Canc Campus, F-94800 Villejuif, France

[5] CIC1428, Gustave Roussy Canc Campus, F-94800 Villejuif, France

[6] Univ Paris Saclay, Serv Biostat & Epidemiol, Gustave Roussy, F-94805 Villejuif, France

[7] St Antoine Hosp, INSERM ERL 1157 CNRS UMR 7203, F-75005 Paris, France

[8] NYU, Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA

[9] Copenhagen Univ Hosp, Dept Hematol & Oncol, Ctr Canc Immune Therapy, DK-2730 Herlev, Denmark

[10] Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, BioMed Res Inst Israel Canada Fac Med, IL-91120 Jerusalem, Israel

[11] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA

[12] Yale Sch Med, Dept Immunobiol, 10 Amistad St, New Haven, CT 06519 USA

[13] Eutilex, Suite 1401 Daeryung Technotown 17 Gasan Digital, Seoul 08594, South Korea

[14] Tulane Univ, Dept Med, Clin Immunol Sect, Sect Clin Immunol Allergy & Rheumatol,Hlth Sci Ct, New Orleans, LA 70112 USA

[15] Brigham & Womens Hosp, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA

[16] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA

[17] Harvard Med Sch, Boston, MA 02115 USA

[18] Univ Med Ctr Tubingen, Dept Dermatol, D-72076 Tubingen, Germany

[19] Univ Franche Comte, Serv Dermatol, CHU, EA3181,SFR4234, F-25000 Besancon, France

[20] Univ Hosp Besancon, Dept Med Oncol, 3 Blvd Alexander Fleming, F-25030 Besancon, France

[21] Univ Hosp Besancon, Clin Invest Ctr, CIC 1431, F-25030 Besancon, France

[22] Univ Franche Comte, INSERM, U1098, F-25020 Besancon, France

[23] Ctr Hosp Lyon Sud, Hosp Civils Lyon, F-69000 Lyon, France

[24] Univ Claude Bernard Lyon 1, F-69000 Lyon, France

[25] Ctr Rech Cancrol Lyon, F-69000 Lyon, France

[26] Hosp Civils Lyon, Dept Pathol, Ctr Hosp Lyon Sud, F-69000 Lyon, France

[27] Dept Pathol, Gustave Roussy Canc Campus, F-94800 Villejuif, France

[28] Univ Hosp Siena, Med Oncol & Immunotherapy Div, Viale Bracci,14, I-53100 Siena, Italy

[29] Univ Hosp Siena, Inst Toscano Tumori, Dept Oncol, Med Oncol & Immunotherapy, I-53100 Siena, Italy

[30] Univ Duisburg Essen, Univ Hosp, Dept Dermatol, Essen, Germany

[31] German Canc Consortium DKTZ, D-69120 Heidelberg, Germany

[32] Ctr Appl Med Res, Div Gene Therapy & Hepatol, Pamplona 31008, Spain

[33] Univ Clin Navarra, Oncol Dept, Pamplona 31008, Spain

[34] Ctr Invest Biomed Red Oncol, Pamplona 31008, Spain

[35] CHU Nantes, Dept Onco Dermatol, CIC Biotherapy, INSERM U1232, F-44000 Nantes, France

[36] Univ Hosp Zurich, Dept Dermatol, CH-8091 Zurich, Switzerland

[37] Univ Zurich, CH-8091 Zurich, Switzerland

[38] Providence Canc Ctr, Earle A Chiles Res Inst, Portland, OR 97213 USA

[39] Hadassah Med Org, Sharett Inst Oncol, IL-91120 Jerusalem, Israel

[40] Aarhus Univ Hosp, Dept Oncol, DK-8200 Aarhus, Denmark

[41] Ctr Rech Cordeliers, INSERM, U1138, F-75006 Paris, France

[42] Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, F-75006 Paris, France

[43] Univ Paris 05, Sorbonne Paris Cite, F-75006 Paris, France

[44] Univ Paris 06, F-75005 Paris, France

[45] Hop Europeen Georges Pompidou, Pole Biol, AP HP, F-75015 Paris, France

[46] Gustave Roussy Canc Ctr, Dept Surg, F-94800 Villejuif, France

[47] Gustave Roussy Canc Ctr, Dept Dermatol, F-94800 Villejuif, France

[48] QIMR Berghofer Med Res Inst, Immunol Canc & Infect Lab, Herston, Qld 4006, Australia

[49] Univ Queensland, Sch Med, Herston, Qld 4006, Australia

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国医学研究理事会;

关键词：

STAGE-III MELANOMA; TUMOR-INFILTRATING LYMPHOCYTES; CIRCULATING SOLUBLE FAS; BREAST-CANCER PATIENTS; CELL LUNG-CANCER; METASTATIC MELANOMA; CLINICAL-SIGNIFICANCE; UNTREATED MELANOMA; COMBINED NIVOLUMAB; PROGNOSTIC IMPACT;

D O I：

10.1038/s41467-017-00608-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页数：13

共 50 条

[1] 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
[J]. Nature Communications, 8
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