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Open AccessArticle

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

1
Biologie du médicament-toxicologie, Hôpital Cochin, AP-HP, 75014 Paris, France
2
UMR8038 CNRS, U1268 INSERM, Faculty of Pharmacy, University Paris Descartes, PRES Sorbonne Paris Cité, 75006 Paris, France
3
Department of Medical Oncology, Hôpital Cochin, AP-HP, 75014 Paris, France
4
Biopathology Department, Institut Curie, 75005 Paris, France
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Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Hôpital Cochin, AP-HP, 75014 Paris, France
6
U1016 INSERM, UMR 8104 CNRS, UMR-S1016, CARPEM, Université Paris Descartes, Sorbonne Paris Cité, 74014 Paris, France
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(6), 762; https://doi.org/10.3390/cancers11060762
Received: 12 April 2019 / Revised: 22 May 2019 / Accepted: 25 May 2019 / Published: 31 May 2019
(This article belongs to the Special Issue New Biomarkers in Cancers)
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® microarrays were used to explore the STK kinomic profile in PBMC from 28 NSCLC patients before nivolumab initiation (D0) and on day 14 (D14) of the first administration. Two clusters of patients (A and B) were identified at D0, 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. View Full-Text
Keywords: nivolumab; kinome; PBMC; non-small-cell lung cancer; immunotherapy nivolumab; kinome; PBMC; non-small-cell lung cancer; immunotherapy
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Noé, G.; Bellesoeur, A.; Golmard, L.; Thomas-Schoemann, A.; Boudou-Rouquette, P.; Tiako Meyo, M.; Puszkiel, A.; Arrondeau, J.; Alexandre, J.; Goldwasser, F.; Blanchet, B.; Vidal, M. Differential Kinase Activation in Peripheral Blood Mononuclear Cells from Non-Small-Cell Lung Cancer Patients Treated with Nivolumab. Cancers 2019, 11, 762.

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