, élargir l'arsenal thérapeutique, notamment avec le nivolumab. Cependant son utilisation chez les sujets âgés a très peu été étudiée lors des études pivots CheckMate 017 et 057. Une étude rétrospective de l

, er février 2015 et le 30 décembre 2018 sur les données de toxicité, d'efficacité et d'arrêts précoces chez le sujet âgé

, De plus notre étude a permis de mettre en avant qu'un IMC faible pouvait être lié à la survenue de toxicité (p = 0,05), de même que les patients présentant des métastases hépatiques étaient moins fréquemment exposés aux toxicités, L'analyse des données de toxicité révèle une fréquence plus importante dans notre population comparativement aux données des études pivots avec notamment des fréquences de toxicité cutanée, vol.2, p.0

, 5 mois vs 2,56 mois) et de SG (11,3 mois vs 11,1 mois) globalement équivalentes. L'analyse multivariée des données de survie met en évidence différents paramètres pouvant influer la réponse au nivolumab : il ressort de cette étude plusieurs facteurs influençant la SSP et la SG : l'utilisation de cisplatine dans les cures, L'analyse des données d'efficacité est comparable aux données des études pivots notamment avec des médianes de SSP

, De même, l'absence d'association d'une antibiothérapie, corticothérapie et/ou IPP au nivolumab ressort comme un facteur protecteur de progression, vol.07, p.0

, Concernant les arrêts précoces, l'analyse multivariée révèle que le nivolumab en 2 ème ligne est un facteur de risque d

, Néanmoins, l'utilisation de cisplatine dans les cures précédant le nivolumab apparaît comme un facteur protecteur d'arrêts précoces

, De plus, certains facteurs biologiques tels qu'un taux de CRP (p = 0,0281), de globules blancs (p = 0,0003) et de polynucléaires neutrophiles

R. L. Siegel, K. D. Miller, and A. Jemal, Cancer statistics, CA Cancer J Clin. févr, vol.66, issue.1, pp.7-30, 2016.

. Dp_cartographie_des_depenses_et_des_pathologies and . Pdf,

D. Sur,

P. C. Tumeh, C. L. Harview, J. H. Yearley, I. P. Shintaku, E. Taylor et al., PD-1 blockade induces responses by inhibiting adaptive immune resistance, Nature, vol.515, issue.7528, pp.568-71, 2014.

, KEYTRUDA (pembrolizumab, p.26

D. Sur,

J. Brahmer, K. L. Reckamp, P. Baas, L. Crinò, W. Eberhardt et al., nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer, N Engl J Med. 9 juill, vol.373, issue.2, pp.123-158, 2015.

H. Borghaei, L. Paz-ares, L. Horn, D. R. Spigel, M. Steins et al., nivolumab versus Docetaxel in Advanced Non-squamous Non-small Cell Lung Cancer, N Engl J Med, vol.373, issue.17, pp.1627-1666, 2015.

K. S. Versteeg, I. R. Konings, A. M. Lagaay, A. A. Van-de-loosdrecht, and H. Verheul, Prediction of treatment-related toxicity and outcome with geriatric assessment in elderly patients with solid malignancies treated with chemotherapy: a systematic review, Ann Oncol Off J Eur Soc Med Oncol, vol.25, issue.10, pp.1914-1922, 2014.

S. Patris, Polymedication among elderly patients Preventing drug related problems and inappropriate medication

, J Pharm Belg. sept, issue.3, pp.4-9, 2016.

, L'Institut publie L'essentiel des faits et chiffres des cancers en France (édition 2019) -Actualités

. Le-cancer-en, France métropolitaine : projections d'incidence et de mortalité par cancer en, 2017.

F. Bigot, L. Verlingue, L. Staudacher, S. Jouveshomme, C. Beuzelin et al., Évolution épidémiologique du cancer broncho-pulmonaire en France et en Europe, Rev Mal Respir Actual. 1 sept, vol.5, issue.5, pp.321-325, 2013.

F. Inca--les-cancers-en,

D. Sur,

, Le cancer du poumon -Les cancers les plus fréquents

D. Sur,

T. Cheng, S. M. Cramb, P. D. Baade, D. R. Youlden, C. Nwogu et al., The International Epidemiology of Lung Cancer: Latest Trends, Disparities, and Tumor Characteristics, J Thorac Oncol Off Publ Int Assoc Study Lung Cancer, vol.11, issue.10, pp.1653-71, 2016.

, Cancer du poumon : points-clés -Cancer du poumon

D. Sur,

P. Goldstraw, J. Crowley, K. Chansky, D. J. Giroux, P. A. Groome et al., The IASLC Lung Cancer Staging Project: Proposals for the Revision of the TNM Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours, J Thorac Oncol. 1 août, vol.2, issue.8, pp.706-720, 2007.

D. Sur, Définition classification TNM

P. Souquet and . Cbnpc, , p.49, 2017.

E. L. Wynder, Tobacco as a cause of lung cancer: some reflections, Am J Epidemiol, vol.146, issue.9, pp.687-94, 1997.

M. Malvezzi, P. Bertuccio, T. Rosso, M. Rota, F. Levi et al., European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women?, Ann Oncol Off J Eur Soc Med Oncol. avr, vol.26, issue.4, pp.779-86, 2015.

J. E. Bailey-wilson, T. A. Sellers, R. C. Elston, C. C. Evens, and H. Rothschild, Evidence for a major gene effect in early-onset lung cancer, J La State Med Soc Off Organ La State Med Soc. avr, vol.145, issue.4, pp.157-62, 1993.

R. Sinha, M. Kulldorff, C. A. Swanson, J. Curtin, R. C. Brownson et al., Dietary heterocyclic amines and the risk of lung cancer among Missouri women, Cancer Res. 15 juill, vol.60, issue.14, pp.3753-3759, 2000.

T. Haldorsen, J. I. Martinsen, K. Kjaerheim, and T. K. Grimsrud, Adjustment for tobacco smoking and alcohol consumption by simultaneous analysis of several types of cancer. Cancer Causes Control CCC, vol.28, pp.155-65, 2017.

R. J. Ginsberg, Lung cancer surgery: acceptable morbidity and mortality, expected results and quality control, Surg Oncol. déc, vol.11, issue.4, pp.263-269, 2002.

, Traitements du cancer du poumon non à petites cellules -Société canad

, Cancer bronchique non à petites cellules -Référentiel national de RCP -Ref : RECOKBRNONPETCEL15 [Internet

L. Käsmann, M. Niyazi, O. Blanck, C. Baues, R. Baumann et al., Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer : A systematic review, Strahlenther Onkol Organ Dtsch Rontgengesellschaft Al, vol.194, issue.2, pp.79-90, 2018.

G. Pilkington, A. Boland, T. Brown, J. Oyee, A. Bagust et al., A systematic review of the clinical effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer, Thorax. avr, vol.70, issue.4, pp.359-67, 2015.

B. Liao, C. Lin, J. Lee, and J. Yang, Optimal management of EGFR-mutant non-small cell lung cancer with disease progression on first-line tyrosine kinase inhibitor therapy, Lung Cancer Amst Neth, vol.110, pp.7-13, 2017.

E. Nadal, B. Massuti, M. Dómine, R. García-campelo, M. Cobo et al., Immunotherapy with checkpoint inhibitors in non-small cell lung cancer: insights from long-term survivors, Cancer Immunol Immunother CII. mars, vol.68, issue.3, pp.341-52, 2019.

D. Sur,

D. Sur,

D. Sur,

. Ct-16457_tecentriq_cbnpc_pic_ins_avis2_ct16457,

D. Sur,

. Ct-17432_imfinzi_pic_ins_avis2_ct17432,

D. Sur,

M. Reck, H. Borghaei, O. Byrne, and K. J. , nivolumab plus ipilimumab in non-small-cell lung cancer, Future Oncol Lond Engl. 8 mai, 2019.

V. Groh, R. Rhinehart, J. Randolph-habecker, M. S. Topp, S. R. Riddell et al., Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells, Nat Immunol. mars, vol.2, issue.3, pp.255-60, 2001.

N. Schleinitz, F. Dignat-george, J. Sampol, J. Harlé, and E. Vivier, Les cellules natural killer, 2008.

D. Sur,

V. Catros-quemener, F. Bouet, and N. Genetet, Immunité anti-tumorale et thérapies cellulaires du cancer. médecine/sciences, janv, vol.19, issue.1, pp.43-53, 2003.

S. Amigorena, Présentation antigénique par les cellules dendritiques. médecine/sciences, vol.15, p.931, 1999.

D. M. Pardoll, Cancer vaccines, Nat Med. mai, vol.4, issue.5, pp.525-556, 1998.

S. Sakaguchi, Regulatory T cells: key controllers of immunologic self-tolerance, Cell. 26 mai, vol.101, issue.5, pp.455-463, 2000.

S. Chouaib, C. Asselin-paturel, F. Mami-chouaib, A. Caignard, and J. Y. Blay, The host-tumor immune conflict: from immunosuppression to resistance and destruction, Immunol Today. oct, vol.18, issue.10, pp.493-500, 1997.

E. C. Ibrahim, N. Guerra, M. J. Lacombe, E. Angevin, S. Chouaib et al., Tumorspecific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma, Cancer Res. 15 sept, vol.61, issue.18, pp.6838-6883, 2001.
URL : https://hal.archives-ouvertes.fr/hal-00092851

R. D. Schreiber, L. J. Old, and M. J. Smyth, Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion, Science. 25 mars, vol.331, issue.6024, pp.1565-70, 2011.

G. P. Dunn, A. T. Bruce, H. Ikeda, L. J. Old, and R. D. Schreiber, Cancer immunoediting: from immunosurveillance to tumor escape, Nat Immunol, vol.3, issue.11, pp.991-999, 2002.

. Guillebon-e-de and E. Tartour, Immunité antitumorale (mécanismes, immunoediting, immunosurveillance), vol.17, 2015.

D. Olive, S. Le-thi, L. Xerri, I. Hirsch, A. Nunès et al., Rôle de CTLA-4 dans la cosignalisation négative du système immunitaire. médecine/sciences, vol.27, pp.842-851, 2011.

M. Larsen, V. Appay, and D. Sauce, Influence de PD-1 sur la synapse immunologique -Une facette de la régulation immunitaire ? médecine/sciences. 1 déc, vol.29, pp.1080-1082, 2013.

P. Vuagnat and S. Champiat, Immunothérapies anti-checkpoints : aspects fondamentaux, MISE AU POINT, vol.6, 2018.

, NCI Dictionary of Cancer Terms, 2011.

D. Sur,

. Ct-16847_opdivo_pis_rcp_avis1_ct16847,

D. Sur,

. Vidal--opdivo, 10 mg/ml sol diluer p perf -Prescription / délivrance / prise en charge

T. Passat, Y. Touchefeu, N. Gervois, A. Jarry, C. Bossard et al., Physiopathological mechanisms of immune-related adverse events induced by anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies in cancer treatment, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-01981595

D. Sur,

J. B. Haanen, .. G. Carbonnel, F. Robert, C. Kerr, K. M. Peters et al., Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Ann Oncol Off J Eur Soc Med Oncol. 1 juill, vol.28, issue.suppl_4, pp.119-161, 2017.

K. Minkis, B. C. Garden, S. Wu, M. P. Pulitzer, and M. E. Lacouture, The risk of rash associated with ipilimumab in patients with cancer: a systematic review of the literature and meta-analysis, J Am Acad Dermatol. sept, vol.69, issue.3, pp.121-128, 2013.

M. Ryder, M. Callahan, M. A. Postow, J. Wolchok, and J. A. Fagin, Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution, Endocr Relat Cancer. avr, vol.21, issue.2, pp.371-81, 2014.

L. Marchand, A. Thivolet, S. Dalle, K. Chikh, S. Reffet et al., Diabetes mellitus induced by PD-1 and PD-L1 inhibitors: description of pancreatic endocrine and exocrine phenotype, Acta Diabetol. avr, vol.56, issue.4, pp.441-449, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02195223

E. E. Vokes, N. Ready, E. Felip, L. Horn, M. A. Burgio et al., nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases, Ann Oncol Off J Eur Soc Med Oncol. 1 avr, vol.29, issue.4, pp.959-65, 2018.

M. Porcu, D. Silva, P. Solinas, C. Battaglia, A. Schena et al., Immunotherapy Associated Pulmonary Toxicity: Biology Behind Clinical and Radiological Features. Cancers. 5 mars, vol.11, issue.3, 2019.

T. K. Eigentler, J. C. Hassel, C. Berking, J. Aberle, O. Bachmann et al., Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy, Cancer Treat Rev. avr, vol.45, pp.7-18, 2016.

, Les inhibiteurs des points de contrôle de l immunité -PDF

D. Sur,

L. Horn, D. R. Spigel, E. E. Vokes, E. Holgado, N. Ready et al., nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057), J Clin Oncol Off J Am Soc Clin Oncol. 10 déc, vol.35, issue.35, pp.3924-3957, 2017.

D. P. Carbone, M. Reck, L. Paz-ares, B. Creelan, L. Horn et al., First-Line nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer, N Engl J Med, vol.22, issue.25, pp.2415-2441, 2017.

H. Borghaei, M. D. Hellmann, L. G. Paz-ares, S. S. Ramalingam, M. Reck et al., Nivo) + platinum-doublet chemotherapy (Chemo) vs chemo as first-line (1L) treatment (Tx) for advanced non-small cell lung cancer (NSCLC) with <1% tumor PD-L1 expression: Results from CheckMate 227, J Clin Oncol. 20 mai, vol.36, issue.15_suppl, pp.9001-9001, 2018.

D. Spigel, L. Schwartzberg, D. Waterhouse, J. Chandler, M. Hussein et al., 02c-026 Is nivolumab Safe and Effective in Elderly and PS2 Patients with Non-Small Cell Lung Cancer (NSCLC)? Results of CheckMate 153, J Thorac Oncol. janv, vol.12, issue.1, pp.1287-1295, 2017.

S. Popat, A. Ardizzoni, T. Ciuleanu, C. Dols, M. Laktionov et al., 1303PDnivolumab in previously treated patients with metastatic squamous NSCLC: Results of a European single-arm, phase 2 trial (CheckMate 171) including patients aged ?70 years and with poor performance status, Ann Oncol, issue.1, 2017.

, NHIS -Adult Tobacco Use -Glossary

D. Sur,

R. Sabatier, N. E. Paciencia, M. , J. Madroszyk, A. Cecile et al., nivolumab in routine practice for older patients with advanced or metastatic non-small cell lung cancer, J Geriatr Oncol. sept, vol.9, issue.5, pp.494-500, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02152681

X. Zhao, S. Suryawanshi, M. Hruska, Y. Feng, X. Wang et al., Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors, Ann Oncol Off J Eur Soc Med Oncol. 1 août, vol.28, issue.8, pp.2002-2010, 2017.

A. F. Mesquita, E. C. Silva, . Da, M. Eickemberg, A. Roriz et al., Factors associated with sarcopenia in institutionalized elderly. Nutr Hosp. 30 mars, vol.34, pp.345-51, 2017.

V. Heidelberger, F. Goldwasser, N. Kramkimel, A. Jouinot, O. Huillard et al., Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients, Invest New Drugs, vol.35, issue.4, pp.436-477, 2017.

A. M. Afzali, T. Müntefering, H. Wiendl, S. G. Meuth, and T. Ruck, Skeletal muscle cells actively shape (auto)immune responses, Autoimmun Rev. mai, vol.17, issue.5, pp.518-547, 2018.

O. Krief, J. , H. De-tauriers, P. Dumenil, C. Neveux et al., Role of antibiotic use, plasma citrulline and blood microbiome in advanced non-small cell lung cancer patients treated with nivolumab, J Immunother Cancer. 10 juill, vol.7, issue.1, p.176, 2019.

, Les antibiotiques perturbent l'efficacité de l'immunothérapie

. Salle-de-presse-|-inserm, , 2017.

B. Routy, L. Chatelier, E. Derosa, L. Duong, C. Alou et al., Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors, Science. 5 janv, vol.359, issue.6371, pp.91-98, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01727917

L. Derosa, M. D. Hellmann, M. Spaziano, D. Halpenny, M. Fidelle et al., Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer, Ann Oncol Off J Eur Soc Med Oncol. 1 juin, vol.29, issue.6, pp.1437-1481, 2018.

S. C. Scott and N. A. Pennell, Early Use of Systemic Corticosteroids in Patients with Advanced NSCLC Treated with nivolumab, J Thorac Oncol Off Publ Int Assoc Study Lung Cancer, vol.13, issue.11, pp.1771-1776, 2018.

M. Bernal, G. Mezquita, L. Auclin, E. Ferrara, R. Planchard et al., 1323PBaseline corticosteroids (CS) could be associated with absence of benefit to immune checkpoint inhibitors (ICI) in advanced non-small cell lung cancer (NSCLC) patients, Ann Oncol, issue.1, 2017.

, Efficacy of PD-1/PD-L1 therapy: Do proton pump inhibitors affect the outcome?, Journal of Clinical Oncology, vol.86

, PPIS Therapy Negatively Impacts the Efficacy of nivolumab | ESMO

D. Sur,

T. F. Nishijima, H. B. Muss, S. S. Shachar, and S. J. Moschos, Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: A systematic review and meta-analysis, Cancer Treat Rev. avr, vol.45, pp.30-37, 2016.

P. O. Lang and R. Aspinall, Immunosenescence and herd immunity: with an ever-increasing aging population do we need to rethink vaccine schedules?, Expert Rev Vaccines. févr, vol.11, issue.2, pp.167-76, 2012.

R. Aspinall, D. Pitts, A. Lapenna, and W. Mitchell, Immunity in the elderly: the role of the thymus, J Comp Pathol. janv, vol.142, issue.1, pp.111-115, 2010.

S. Ferrando-martínez, E. Ruiz-mateos, A. Hernández, E. Gutiérrez, M. Rodríguez-méndez-m-del et al., Age-related deregulation of naive T cell homeostasis in elderly humans, Age. juin, vol.33, issue.2, pp.197-207, 2011.

R. B. Effros, Role of T lymphocyte replicative senescence in vaccine efficacy, Vaccine. 8 janv, vol.25, issue.4, pp.599-604, 2007.

A. Wikby, F. Ferguson, R. Forsey, J. Thompson, J. Strindhall et al., An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans, J Gerontol A Biol Sci Med Sci. mai, vol.60, issue.5, pp.556-65, 2005.

O. Briceño, A. Lissina, K. Wanke, G. Afonso, A. Von-braun et al., Reduced naïve CD8+ T-cell priming efficacy in elderly adults, Aging Cell. févr, vol.15, issue.1, pp.14-21, 2016.

L. Seymour, J. Bogaerts, A. Perrone, R. Ford, L. H. Schwartz et al., iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics, Lancet Oncol, vol.18, issue.3, pp.143-52, 2017.

A. Costantini, V. Fallet, J. Corny, S. Friard, C. Chouaid et al., nivolumabrefractory patients with advanced non-small-cell lung cancer, Lung Cancer Amst Neth. avr, vol.130, pp.128-162, 2019.

R. Ferrara, L. Mezquita, M. Texier, J. Lahmar, C. Audigier-valette et al., Hyperprogressive Disease in Patients With Advanced Non-Small Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or With Single-Agent Chemotherapy, JAMA Oncol, vol.4, issue.11, pp.1543-52, 2018.

Y. Taniguchi, A. Tamiya, S. Isa, K. Nakahama, K. Okishio et al., Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with nivolumab, Anticancer Res, vol.37, issue.10, pp.5857-62, 2017.

S. J. Bagley, S. Kothari, C. Aggarwal, J. M. Bauml, E. W. Alley et al., Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer, Lung Cancer. 1 avr, vol.106, pp.1-7, 2017.

H. West, ). Jack, and J. O. Jin, Performance Status in Patients With Cancer, JAMA Oncol, vol.1, issue.7, pp.998-998, 2015.

O. Kanai, K. Fujita, M. Okamura, K. Nakatani, and T. Mio, Severe exacerbation or manifestation of primary disease related to nivolumab in non-small-cell lung cancer patients with poor performance status or brain metastases, Ann Oncol. 1 juill, vol.27, issue.7, pp.1354-1360, 2016.

S. J. Bagley, S. Kothari, C. Aggarwal, J. M. Bauml, E. W. Alley et al., Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer, Lung Cancer Amst Neth, vol.106, pp.1-7, 2017.

R. Zahorec, Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill, Bratisl Lek Listy, vol.102, issue.1, pp.5-14, 2001.

F. Donskov, Immunomonitoring and prognostic relevance of neutrophils in clinical trials, Semin Cancer Biol. 1 juin, vol.23, issue.3, pp.200-207, 2013.

Y. Nakamura, S. Kitano, A. Takahashi, A. Tsutsumida, K. Namikawa et al., nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy, Oncotarget, vol.22, issue.47, pp.77404-77419, 2016.

Y. Oya, T. Yoshida, H. Kuroda, M. Mikubo, C. Kondo et al., Predictive clinical parameters for the response of nivolumab in pretreated advanced non-small-cell lung cancer, Oncotarget, vol.8, issue.61, pp.103117-103145, 2017.

H. Tang, Y. Bai, W. Shen, and J. Zhao,

, Zhejiang Xue Xue Bao Yi Xue Ban, J Zhejiang Univ Med Sci. 25 déc, vol.47, issue.6, pp.659-64, 2018.

T. Inoue, M. Tamiya, A. Tamiya, K. Nakahama, Y. Taniguchi et al., Analysis of Early Death in Japanese Patients With Advanced Non-small-cell Lung Cancer Treated With nivolumab, Clin Lung Cancer, vol.19, issue.2, pp.171-177, 2018.

F. Zhang, L. Ying, J. J. Chen, K. Zhang, N. Wu et al., The C-reactive protein/albumin ratio predicts long-term outcomes of patients with operable non-small cell lung cancer, Oncotarget. 31 janv, vol.8, issue.5, pp.8835-8877, 2017.