Biomarkers associated with checkpoint inhibitors

被引：134

作者：

Manson, G. ^{[1
]}

Norwood, J. ^{[1
]}

Marabelle, A. ^{[2
,3
]}

Kohrt, H. ^{[4
]}

Houot, R. ^{[1
,5
]}

机构：

[1] CHU Rennes, Dept Hematol, 2 Rue Henri Le Guilloux, F-35033 Rennes 9, France

[2] DITEP, Dept Drug Dev, Gustave Roussy Canc Campus GRCC, Villejuif, France

[3] Gustave Roussy Canc Inst, INSERM, U1015, Villejuif, France

[4] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA

[5] INSERM, U917, Rennes, France

来源：

ANNALS OF ONCOLOGY | 2016年 / 27卷 / 07期

关键词：

biomarkers; checkpoint inhibitors; cancer; immunotherapy; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; ADVANCED MELANOMA PATIENTS; EXPANDED ACCESS PROGRAM; REGULATORY T-CELLS; CTLA-4; BLOCKADE; IPILIMUMAB TREATMENT; METASTATIC MELANOMA; CLINICAL-RESPONSE; SUPPRESSOR-CELLS; IFN-GAMMA;

D O I：

10.1093/annonc/mdw181

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Numerous biomarkers may reflect the pharmacodynamics of checkpoint inhibitors and predict their efficacy and/or their toxicity in patients. However, the interest of these biomarkers in clinical practice remains ill-defined and will have to be clarified in future studies. Such biomarkers should help to finely define patients who will benefit most from these costly and potentially toxic drugs.Checkpoint inhibitors (CPI), namely anti-CTLA4 and anti-PD1/PD-L1 antibodies, demonstrated efficacy across multiple types of cancer. However, only subgroups of patients respond to these therapies. Additionally, CPI can induce severe immune-related adverse events (irAE). Biomarkers that predict efficacy and toxicity may help define the patients who may benefit the most from these costly and potentially toxic therapies. In this study, we review the main biomarkers that have been associated with the efficacy (pharmacodynamics and clinical benefit) and the toxicity (irAE) of CPIs in patients.

引用

页码：1199 / 1206

页数：8

共 72 条

[1] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[2]

[Anonymous], 2014, J TRANSL MED

[3] Clinical experience with ipilimumab 3 mg/kg: real-world efficacy and safety data from an expanded access programme cohort [J].

Ascierto, Paolo A. ;

Simeone, Ester ;

Sileni, Vanna Chiarion ;

Pigozzo, Jacopo ;

Maio, Michele ;

Altomonte, Maresa ;

Del Vecchio, Michele ;

Di Guardo, Lorenza ;

Marchetti, Paolo ;

Ridolfi, Ruggero ;

Cognetti, Francesco ;

Testori, Alessandro ;

Bernengo, Maria Grazia ;

Guida, Michele ;

Marconcini, Riccardo ;

Mandala, Mario ;

Cimminiello, Carolina ;

Rinaldi, Gaetana ;

Aglietta, Massimo ;

Queirolo, Paola .

JOURNAL OF TRANSLATIONAL MEDICINE, 2014, 12

[4] Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4 [J].

Attia, P ;

Phan, GQ ;

Maker, AV ;

Robinson, MR ;

Quezado, MM ;

Yang, JC ;

Sherry, RM ;

Topalian, SL ;

Kammula, US ;

Royal, RE ;

Restifo, NP ;

Haworth, LR ;

Levy, C ;

Mavroukakis, SA ;

Nichol, G ;

Yellin, MJ ;

Rosenberg, SA .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (25) :6043-6053

[5] Final Version of 2009 AJCC Melanoma Staging and Classification [J].

Balch, Charles M. ;

Gershenwald, Jeffrey E. ;

Soong, Seng-jaw ;

Thompson, John F. ;

Atkins, Michael B. ;

Byrd, David R. ;

Buzaid, Antonio C. ;

Cochran, Alistair J. ;

Coit, Daniel G. ;

Ding, Shouluan ;

Eggermont, Alexander M. ;

Flaherty, Keith T. ;

Gimotty, Phyllis A. ;

Kirkwood, John M. ;

McMasters, Kelly M. ;

Mihm, Martin C., Jr. ;

Morton, Donald L. ;

Ross, Merrick I. ;

Sober, Arthur J. ;

Sondak, Vernon K. .

JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (36) :6199-6206

[6]

Beavis PA, 2015, ONCOIMMUNOLOGY, V4

[7]

Berman DM, 2009, J CLIN ONCOL, V27

[8]

Berman David, 2010, Cancer Immun, V10, P11

[9]

Callahan MK, 2011, J CLIN ONCOL S, V29, P2011

[10] Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers [J].

Carbognin, Luisa ;

Pilotto, Sara ;

Milella, Michele ;

Vaccaro, Vanja ;

Brunelli, Matteo ;

Calio, Anna ;

Cuppone, Federica ;

Sperduti, Isabella ;

Giannarelli, Diana ;

Chilosi, Marco ;

Bronte, Vincenzo ;

Scarpa, Aldo ;

Bria, Emilio ;

Tortora, Giampaolo .

PLOS ONE, 2015, 10 (06)

← 1 2 3 4 5 6 7 8 →