Differential Kinase Activation in Peripheral Blood Mononuclear Cells from Non-Small-Cell Lung Cancer Patients Treated with Nivolumab

被引：5

作者：

Noe, Gaelle ^{[1
,2
]}

Bellesoeur, Audrey ^{[2
,3
]}

Golmard, Lisa ^{[4
]}

Thomas-Schoemann, Audrey ^{[1
,2
,5
]}

Boudou-Rouquette, Pascaline ^{[3
,5
]}

Meyo, Manuela Tiako ^{[2
]}

Puszkiel, Alicja ^{[1
]}

Arrondeau, Jennifer ^{[3
,5
]}

Alexandre, Jerome ^{[3
,5
,6
]}

Goldwasser, Francois ^{[3
,5
,6
]}

Blanchet, Benoit ^{[1
,2
,5
]}

Vidal, Michel ^{[1
,2
,5
]}

机构：

[1] Hop Cochin, AP HP, Biol Medicament Toxicol, F-75014 Paris, France

[2] Univ Paris 05, PRES Sorbonne Paris Cite, Fac Pharm, UMR8038 CNRS,U1268 INSERM, F-75006 Paris, France

[3] Hop Cochin, AP HP, Dept Med Oncol, F-75014 Paris, France

[4] Inst Curie, Biopathol Dept, F-75005 Paris, France

[5] Hop Cochin, AP HP, Immunomodulatory Therapies Multidisciplinary Stud, F-75014 Paris, France

[6] Univ Paris 05, Sorbonne Paris Cite, CARPEM, U1016 INSERM,UMR 8104 CNRS,UMR 51016, F-74014 Paris, France

来源：

CANCERS | 2019年 / 11卷 / 06期

关键词：

nivolumab; kinome; PBMC; non-small-cell lung cancer; immunotherapy; LYMPHOCYTE RATIO NLR; RECTAL-CANCER; STAGE IV; DOCETAXEL; NSCLC; PD-1; CHEMOTHERAPY; CHECKPOINTS; NEUTROPHIL; EXPRESSION;

D O I：

10.3390/cancers11060762

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In the era of precision medicine, research of biomarkers for identification of responders to nivolumab therapy is a major challenge. Peripheral blood mononuclear cells (PBMC) could be an interesting surrogate tissue for identifying pharmacodynamic biomarkers. The aim of this exploratory study was to investigate the global serine/threonine kinase (STK) activity in PBMC from non-small-cell lung cancer (NSCLC) patients using a high throughput kinomic profiling method. PamChip (R) microarrays were used to explore the STK kinomic profile in PBMC from 28 NSCLC patients before nivolumab initiation (DO) and on day 14 (D14) of the first administration. Two clusters of patients (A and B) were identified at DO, median overall survival (OS) tended to be longer in cluster A than in B (402 vs. 112.5 days, respectively; p = 0.15). Interestingly, the PD-L1 tumor cell score (p = 0.045), the count of CD8+ cells (p = 0.023) and the total body weight (p = 0.038) were statistically different between the clusters. On D14, clusters C and D were identified. Greater activity of most STK, especially those of the PI3K/Akt signaling pathway, was noticed among cluster C. No significant difference between C and D was observed regarding OS. Considering the small number of patients, results from this preliminary study are not conclusive. However, the 4-fold longer median OS in cluster A paves the way to further investigate, in a larger cohort of NSCLC patients, the benefit of basal STK kinomic profile in PBMC to identify responders to nivolumab therapy.

引用

页数：15

共 36 条

[1] IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer [J].

Abiko, K. ;

Matsumura, N. ;

Hamanishi, J. ;

Horikawa, N. ;

Murakami, R. ;

Yamaguchi, K. ;

Yoshioka, Y. ;

Baba, T. ;

Konishi, I. ;

Mandai, M. .

BRITISH JOURNAL OF CANCER, 2015, 112 (09) :1501-1509

[2]

Anderson Joshua C, 2015, Med Res Arch, V2015, DOI 10.18103/mra.v0i3.104

[3] High Throughput Kinomic Profiling of Human Clear Cell Renal Cell Carcinoma Identifies Kinase Activity Dependent Molecular Subtypes [J].

Anderson, Joshua C. ;

Willey, Christopher D. ;

Mehta, Amitkumar ;

Welaya, Karim ;

Chen, Dongquan ;

Duarte, Christine W. ;

Ghatalia, Pooja ;

Arafat, Waleed ;

Madan, Ankit ;

Sudarshan, Sunil ;

Naik, Gurudatta ;

Grizzle, William E. ;

Choueiri, Toni K. ;

Sonpavde, Guru .

PLOS ONE, 2015, 10 (09)

[4] Kinomic Profiling of Electromagnetic Navigational Bronchoscopy Specimens: A New Approach for Personalized Medicine [J].

Anderson, Joshua C. ;

Minnich, Douglas J. ;

Dobelbower, M. Christian ;

Denton, Alexander J. ;

Dussaq, Alex M. ;

Gilbert, Ashley N. ;

Rohrbach, Timothy D. ;

Arafat, Waleed ;

Welaya, Karim ;

Bonner, James A. ;

Willey, Christopher D. .

PLOS ONE, 2014, 9 (12)

[5] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[6] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].

Brahmer, Julie ;

Reckamp, Karen L. ;

Baas, Paul ;

Crino, Lucio ;

Eberhardt, Wilfried E. E. ;

Poddubskaya, Elena ;

Antonia, Scott ;

Pluzanski, Adam ;

Vokes, Everett E. ;

Holgado, Esther ;

Waterhouse, David ;

Ready, Neal ;

Gainor, Justin ;

Aren Frontera, Osvaldo ;

Havel, Libor ;

Steins, Martin ;

Garassino, Marina C. ;

Aerts, Joachim G. ;

Domine, Manuel ;

Paz-Ares, Luis ;

Reck, Martin ;

Baudelet, Christine ;

Harbison, Christopher T. ;

Lestini, Brian ;

Spigel, David R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135

[7] First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer [J].

Carbone, D. P. ;

Reck, M. ;

Paz-Ares, L. ;

Creelan, B. ;

Horn, L. ;

Steins, M. ;

Felip, E. ;

van den Heuvel, M. M. ;

Ciuleanu, T. -E. ;

Badin, F. ;

Ready, N. ;

Hiltermann, T. J. N. ;

Nair, S. ;

Juergens, R. ;

Peters, S. ;

Minenza, E. ;

Wrangle, J. M. ;

Rodriguez-Abreu, D. ;

Borghaei, H. ;

Blumenschein, G. R. ;

Villaruz, L. C. ;

Havel, L. ;

Krejci, J. ;

Corral Jaime, J. ;

Chang, H. ;

Geese, W. J. ;

Bhagavatheeswaran, P. ;

Chen, A. C. ;

Socinski, M. A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (25) :2415-2426

[8] Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer [J].

Cedres, S. ;

Torrejon, D. ;

Martinez, A. ;

Martinez, P. ;

Navarro, A. ;

Zamora, E. ;

Mulet-Margalef, N. ;

Felip, E. .

CLINICAL & TRANSLATIONAL ONCOLOGY, 2012, 14 (11) :864-869

[9] Characterization of the in vivo immune network of IDO, tryptophan metabolism, PD-L1, and CTLA-4 in circulating immune cells in melanoma [J].

Chevolet, I. ;

Speeckaert, R. ;

Schreuer, M. ;

Neyns, B. ;

Krysko, O. ;

Bachert, C. ;

Hennart, B. ;

Allorge, D. ;

van Geel, N. ;

Van Gele, M. ;

Brochez, L. .

ONCOIMMUNOLOGY, 2015, 4 (03) :1-8

[10] Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma [J].

Choueiri, Toni K. ;

Fishman, Mayer N. ;

Escudier, Bernard ;

McDermott, David F. ;

Drake, Charles G. ;

Kluger, Harriet ;

Stadler, Walter M. ;

Perez-Gracia, Jose Luis ;

McNeel, Douglas G. ;

Curti, Brendan ;

Harrison, Michael R. ;

Plimack, Elizabeth R. ;

Appleman, Leonard ;

Fong, Lawrence ;

Albiges, Laurence ;

Cohen, Lewis ;

Young, Tina C. ;

Chasalow, Scott D. ;

Ross-Macdonald, Petra ;

Srivastava, Shivani ;

Jure-Kunkel, Maria ;

Kurland, John F. ;

Simon, Jason S. ;

Sznol, Mario .

CLINICAL CANCER RESEARCH, 2016, 22 (22) :5461-5471

← 1 2 3 4 →