免疫检查点阻断抗体的不良反应研究进展
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摘要
免疫检查点阻断治疗是通过解除肿瘤细胞或其他免疫细胞上共抑制性分子对T细胞的抑制,从而恢复T细胞抗肿瘤免疫反应的治疗策略。程序性死亡受体-1、细胞毒性T淋巴细胞抗原-4作为研究最热的免疫检查点信号分子,其相应的阻断抗体在抗肿瘤临床治疗取得辉煌成果,并已被批准用于多种肿瘤的治疗。免疫相关副作用是免疫检查点抗体药物治疗过程中伴随出现的治疗目的以外的药理作用,鉴于免疫检查点抗体药物的广泛应用,有必要探讨免疫相关副作用的诊断及相应的处置方法。
Immune checkpoint therapy is a therapeutic strategy that restores T cell anti-tumor immune responses by relieving T cell suppression by tumor suppressor molecules on tumor cells or other immune cells. Programmed death receptor-1 and cytotoxic T lymphocyte antigen-4 as the main immune checkpoint signal molecules,its corresponding blocking antibody has achieved brilliant results in clinical treatment,and has been approved for a variety of treatment of tumors. Immune-related side effects are the pharmacological effects beyond the therapeutic purposes that accompany the immune checkpoint antibody drug treatment. Given the widespread use of immune checkpoint antibodies,it is necessary to investigate the diagnosis of immune-related side effects and the corresponding disposal methods.
Immune checkpoint therapy is a therapeutic strategy that restores T cell anti-tumor immune responses by relieving T cell suppression by tumor suppressor molecules on tumor cells or other immune cells. Programmed death receptor-1 and cytotoxic T lymphocyte antigen-4 as the main immune checkpoint signal molecules,its corresponding blocking antibody has achieved brilliant results in clinical treatment,and has been approved for a variety of treatment of tumors. Immune-related side effects are the pharmacological effects beyond the therapeutic purposes that accompany the immune checkpoint antibody drug treatment. Given the widespread use of immune checkpoint antibodies,it is necessary to investigate the diagnosis of immune-related side effects and the corresponding disposal methods.
引文
[1]Afzal MZ,Mabaera R,Shirai K. Metastatic uveal melanoma showing durable response to anti-CTLA-4 and anti-PD-1 combination therapy after experiencing progression on anti-PD-1 therapy alone[J]. J Immunother Cancer,2018,6(1):13.
[2]Pintova S,Sidhu H,Friedlander PA,et al. Sweet's syndrome in a patient with metastatic melanoma after ipilimumab therapy[J]. Melanoma Res,2013,23(6):498-501.
[3]Postow MA,Callahan MK,Wolchok JD. Immune Checkpoint Blockade in Cancer Therapy[J]. J Clin Oncol,2015,33(17):1974-1982.
[4]Marconcini R,Spagnolo F,Stucci LS,et al. Current status and perspectives in immunotherapy for metastatic melanoma[J]. Oncotarget,2018,9(15):12452-12470.
[5]Scott LJ. Nivolumab:A Review in Advanced Melanoma[J]. Drugs,2015,75(12):1413-1424.
[6]Garcia-Neuer M,Marmarelis ME,Jangi SR,et al. Diagnostic Comparison of CT Scans and Colonoscopy for Immune-Related Colitis in Ipilimumab-Treated Advanced Melanoma Patients[J]. Cancer Immunol Res,2017,5(4):286-291.
[7]Sanford M. Ipilimumab:in previously treated patients with advanced melanoma[J]. BioDrugs,2012,26(3):185-193.
[8]Wolchok JD,Neyns B,Linette G,et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma:a randomised,doubleblind,multicentre,phase 2,dose-ranging study[J]. Lancet Oncol,2010,11(2):155-164.
[9]Hu H,Zhu Q,Luo XS,et al. Efficacy of PD-1/PD-L1 inhibitors against pretreated advanced cancer:a systematic review and meta-analysis[J]. Oncotarget,2018,9(14):11846-11857.
[10]Hamid O,Robert C,Daud A,et al. Safety and tumor responses with lambrolizumab(anti-PD-1)in melanoma[J]. N Engl J Med,2013,369(2):134-144.
[11]Pages C,Gornet JM,Monsel G,et al. Ipilimumab-induced acute severe colitis treated by infliximab[J]. Melanoma Res,2013,23(3):227-230.
[12]Weber JS,Khler KC,Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab[J]. J Clin Oncol,2012,30(21):2691-2697.
[13]Puzanov I,Diab A,Abdallah K,et al. Managing toxicities associated with immune checkpoint inhibitors:consensus recommendations from the Society for Immunotherapy of Cancer(SITC)Toxicity Management Working Group[J]. J Immunother Cancer,2017,5(1):95.
[14]Clarke JM,George DJ,Lisi S,et al. Immune Checkpoint Blockade:The New Frontier in Cancer Treatment[J]. Target Oncol,2018,13(1):1-20.
[15]Ribas A,Kefford R,Marshall MA,et al. PhaseⅢrandomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma[J]. J Clin Oncol,2013,31(5):616-622.
[16]Bernardo SG,Moskalenko M,Pan M,et al. Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma[J]. Melanoma Res,2013,23(1):47-54.
[17]Chmiel KD,Suan D,Liddle C,et al. Resolution of severe ipilimumabinduced hepatitis after antithymocyte globulin therapy[J]. J Clin Oncol,2011,29(9):237-240.
[18]Bernardo SG,Moskalenko M,Pan M,et al. Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma[J]. Melanoma Res,2013,23(1):47-54.
[19]Sanjeevaiah A,Kerr T,Beg MS. Approach and management of checkpoint inhibitor-related immune hepatitis[J]. J Gastrointest Oncol,2018,9(1):220-224.
[20]Chmiel KD,Suan D,Liddle C,et al. Resolution of Severe IpilimumabInduced Hepatitis After Antithymocyte Globulin Therapy[J]. J Clin Oncol,2011,29(9):237-240.
[21]Corsello SM,Barnabei A,Marchetti P,et al. Endocrine side effects induced by immune checkpoint inhibitors[J]. J Clin Endocrinol Metab,2013,98(4):1361-1375.
[22]Sznol M,Postow MA,Davies MJ,et al. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management[J]. Cancer Treat Rev,2017,58:70-76.
[23]Iwama S,Arima H. Clinical practice and mechanism of endocrinological adverse events associated with immune checkpoint inhibitors[J].Nihon Rinsho Meneki Gakkai Kaishi,2017,40(2):90-94.
[24]Vazquez A. Hypophysitis:Nursing Management of Immune-Related Adverse Events[J]. Clin J Oncol Nurs,2017,21(2):154-156.
[25]Okano Y,Satoh T,Horiguchi K,et al. Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma[J]. Endocr J,2016,63(10):905-912.
[26]Torino F,Barnabei A,Paragliola RM,et al. Endocrine side-effects of anti-cancer drugs:m Abs and pituitary dysfunction:clinical evidence and pathogenic hypotheses[J]. Eur J Endocrinol,2013,169(6):153-164.
[27]Blansfield JA,Beck KE,Tran K,et al. Cytotoxic T-Lymphocyte Associated Antigen-4 Blockage Can Induce Autoimmune Hypophysitis in Patients With Metastatic Melanoma and Renal Cancer[J]. J Immunother,2005,28(6):593-598.
[28]Ray A,Williams MA,Meek SM,et al. A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma[J]. Oncologist,2016,7(39):64390-64399.
[29]Sarnaik AA,Yu B,Yu D,et al. Extended Dose Ipilimumab with a Peptide Vaccine:Immune Correlates Associated with Clinical Benefit in Patients with Resected High-Risk StageⅢc/ⅣMelanoma[J].Clinical Cancer Research,2010,17(4):896-906.
[30]Friedman CF,Proverbs-Singh TA,Postow MA. Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors[J].JAMA Oncology,2016,2(10):1346-1353.
[31]Tirumani SH,Ramaiya NH,Keraliya A,et al. Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab[J]. Cancer Immunology Research,2015,3(10):1185-1192.
[32]Nishino M,Sholl LM,Hodi FS,et al. Anti-PD-1-related pneumonitis during cancer immunotherapy[J]. N Engl J Med,2015,373(3):286-288.
[33]Wang C,Yu X,Wang W. A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer[J]. Medicine(Baltimore),2016,95(52):e5539.
[34]Ciccarese C,Alfieri S,Santoni M,et al. New toxicity profile for novel immunotherapy agents:focus on immune-checkpoint inhibitors[J]. J Clin Oncol,2016,12(1):57-75.
[35]Gullo. Day-to-Day Variations of Serum Pancreatic Enzymes in Benign Pancreatic Hyperenzymemia[J]. Clin Gastroenterol Hepatol,2007,5(1):70-74.
[36]Alabed YZ,Aghayev A,Sakellis C,et al. Pancreatitis Secondary to Anti–Programmed Death Receptor 1 Immunotherapy Diagnosed by FDG PET/CT[J]. Clinical Nuclear Medicine,2015,40(11):528-529.
[37]Wilgenhof S,Neyns B,et al. Anti-CTLA-4 antibody-induced Guillain Barre syndrome in a melanoma patient[J]. Ann Oncol,2011,22(4):991-993.
[38]Morello S,Capone M,Sorrentino C,et al. Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab[J]. J Transl Med,2017,15(1):244.
[39]Kumar V,Chaudhary N,Garg M,et al. Current Diagnosis and Management of Immune Related Adverse Events(ir AEs)Induced by Immune Checkpoint Inhibitor Therapy[J]. Front Pharmacol,2017,8:49.
[40]Wilson MA,Guld K,Galetta S,et al. Acute visual loss after ipilimumab treatment for metastatic melanoma[J]. J Immunother Cancer,2016,4:66.
[41]Abdel-Wahab N,Shah M,Lopez-Olivo MA,et al. Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease:A Systematic Review[J]. Ann Intern Med,2018,168(2):121-130.
[42]Dan D,Tapparel L,Hugle T. Rheumatology. Checkpoint-induced autoimmunity-birth of a new disease[J]. Rev Med Suisse,2018,14(588):93-96.
[43]Ponisch W,Alten R,Baerwald C. Autoimmune reactions to immune checkpoint inhibitors[J]. Z Rheumatol,2017,76(2):57-62.
[44]Ott PA,Hodi FS,Kaufman HL,et al. Combination immunotherapy:a road map[J]. J Immunother Cancer,2017,5(1):1-16.
[45]Turajlic S,Gore M,Larkin J. First report of overall survival for ipilimumab plus nivolumab from the phaseⅢCheckmate 067 study in advanced melanoma[J]. Ann Oncol,2018,29(3),542-543.
[46]Callahan MK,Kluger H,Postow MA,et al. Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma:Updated Survival,Response,and Safety Data in a Phase I Dose-Escalation Study[J]. J Clin Oncol,2018,36(4):391-398.
[47]Wolchok JD,Chiarion-Sileni V,Gonzalez R,et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma[J]. N Engl J Med,2017,377(14):1345-1356.
[48]Sachpekidis C,Hassel JC,Dimitrakopoulou-Strauss A. Metastatic melanoma response to combination therapy with ipilimumab and vemurafenib[J]. Hell J Nucl Med,2017,20(3):251-253.
[49]Lyseng-Williamson,KA. Ipilimumab:a guide to its use in advanced melanoma in the EU[J]. Drugs Ther Perspect,2014,30(4):124-129.
[50]Chesney J,Imbert-Fernandez Y,Telang S,et al. Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors[J]. Melanoma Res,2018.
[51]Lang BM,Peveling-Oberhag A,Faidt D,et al. Long-term survival with modern therapeutic agents against metastatic melanoma-vemurafenib and ipilimumab in a daily life setting[J]. Med Oncol. 2018,35(3):24-35.
[52]Brzozowska M,Wierzba W,liwczyński A,et al. Analysis of survival of patients treated with vemurafenib,ipilimumab and dabrafenib for advanced skin melanoma in daily clinical practice(Real-World Data):retrospective analysis of patients treated under drug/reimbursement programmes in Poland in 2013~2016[J]. Melanoma Res,2018,28(1):52-55.
[53]Hoeller C,Michielin O,Ascierto PA,et al. Systematic review of the use of granulocyte-macrophage colony-stimulating factor in patients with advanced melanoma[J]. Cancer Immunol Immunother,2016,65(9):1015-1034.
[54]Kwek SS,Kahn J,Greaney SK,et al. GM-CSF and ipilimumab therapy in metastatic melanoma:Clinical outcomes and immunologic responses[J]. Oncoimmunology,2015,5(4):e1101204.
[55]van Dodewaard-de Jong JM,Santegoets SJ,van de Ven PM,et al. Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells[J]. Oncoimmunology,2015,5(4):e1105431.
[56]Dbritz J. GM-CSF and the role of myeloid regulatory cells in the pathogenesis and treatment of Crohn's disease[J]. Mol Cell Pediatr,2015,2(1):12-19.
[57]Chuang LS,Villaverde N,Hui KY,et al. A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF[J]. Gastroenterology,2016,151(4):710-723.
[2]Pintova S,Sidhu H,Friedlander PA,et al. Sweet's syndrome in a patient with metastatic melanoma after ipilimumab therapy[J]. Melanoma Res,2013,23(6):498-501.
[3]Postow MA,Callahan MK,Wolchok JD. Immune Checkpoint Blockade in Cancer Therapy[J]. J Clin Oncol,2015,33(17):1974-1982.
[4]Marconcini R,Spagnolo F,Stucci LS,et al. Current status and perspectives in immunotherapy for metastatic melanoma[J]. Oncotarget,2018,9(15):12452-12470.
[5]Scott LJ. Nivolumab:A Review in Advanced Melanoma[J]. Drugs,2015,75(12):1413-1424.
[6]Garcia-Neuer M,Marmarelis ME,Jangi SR,et al. Diagnostic Comparison of CT Scans and Colonoscopy for Immune-Related Colitis in Ipilimumab-Treated Advanced Melanoma Patients[J]. Cancer Immunol Res,2017,5(4):286-291.
[7]Sanford M. Ipilimumab:in previously treated patients with advanced melanoma[J]. BioDrugs,2012,26(3):185-193.
[8]Wolchok JD,Neyns B,Linette G,et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma:a randomised,doubleblind,multicentre,phase 2,dose-ranging study[J]. Lancet Oncol,2010,11(2):155-164.
[9]Hu H,Zhu Q,Luo XS,et al. Efficacy of PD-1/PD-L1 inhibitors against pretreated advanced cancer:a systematic review and meta-analysis[J]. Oncotarget,2018,9(14):11846-11857.
[10]Hamid O,Robert C,Daud A,et al. Safety and tumor responses with lambrolizumab(anti-PD-1)in melanoma[J]. N Engl J Med,2013,369(2):134-144.
[11]Pages C,Gornet JM,Monsel G,et al. Ipilimumab-induced acute severe colitis treated by infliximab[J]. Melanoma Res,2013,23(3):227-230.
[12]Weber JS,Khler KC,Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab[J]. J Clin Oncol,2012,30(21):2691-2697.
[13]Puzanov I,Diab A,Abdallah K,et al. Managing toxicities associated with immune checkpoint inhibitors:consensus recommendations from the Society for Immunotherapy of Cancer(SITC)Toxicity Management Working Group[J]. J Immunother Cancer,2017,5(1):95.
[14]Clarke JM,George DJ,Lisi S,et al. Immune Checkpoint Blockade:The New Frontier in Cancer Treatment[J]. Target Oncol,2018,13(1):1-20.
[15]Ribas A,Kefford R,Marshall MA,et al. PhaseⅢrandomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma[J]. J Clin Oncol,2013,31(5):616-622.
[16]Bernardo SG,Moskalenko M,Pan M,et al. Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma[J]. Melanoma Res,2013,23(1):47-54.
[17]Chmiel KD,Suan D,Liddle C,et al. Resolution of severe ipilimumabinduced hepatitis after antithymocyte globulin therapy[J]. J Clin Oncol,2011,29(9):237-240.
[18]Bernardo SG,Moskalenko M,Pan M,et al. Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma[J]. Melanoma Res,2013,23(1):47-54.
[19]Sanjeevaiah A,Kerr T,Beg MS. Approach and management of checkpoint inhibitor-related immune hepatitis[J]. J Gastrointest Oncol,2018,9(1):220-224.
[20]Chmiel KD,Suan D,Liddle C,et al. Resolution of Severe IpilimumabInduced Hepatitis After Antithymocyte Globulin Therapy[J]. J Clin Oncol,2011,29(9):237-240.
[21]Corsello SM,Barnabei A,Marchetti P,et al. Endocrine side effects induced by immune checkpoint inhibitors[J]. J Clin Endocrinol Metab,2013,98(4):1361-1375.
[22]Sznol M,Postow MA,Davies MJ,et al. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management[J]. Cancer Treat Rev,2017,58:70-76.
[23]Iwama S,Arima H. Clinical practice and mechanism of endocrinological adverse events associated with immune checkpoint inhibitors[J].Nihon Rinsho Meneki Gakkai Kaishi,2017,40(2):90-94.
[24]Vazquez A. Hypophysitis:Nursing Management of Immune-Related Adverse Events[J]. Clin J Oncol Nurs,2017,21(2):154-156.
[25]Okano Y,Satoh T,Horiguchi K,et al. Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma[J]. Endocr J,2016,63(10):905-912.
[26]Torino F,Barnabei A,Paragliola RM,et al. Endocrine side-effects of anti-cancer drugs:m Abs and pituitary dysfunction:clinical evidence and pathogenic hypotheses[J]. Eur J Endocrinol,2013,169(6):153-164.
[27]Blansfield JA,Beck KE,Tran K,et al. Cytotoxic T-Lymphocyte Associated Antigen-4 Blockage Can Induce Autoimmune Hypophysitis in Patients With Metastatic Melanoma and Renal Cancer[J]. J Immunother,2005,28(6):593-598.
[28]Ray A,Williams MA,Meek SM,et al. A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma[J]. Oncologist,2016,7(39):64390-64399.
[29]Sarnaik AA,Yu B,Yu D,et al. Extended Dose Ipilimumab with a Peptide Vaccine:Immune Correlates Associated with Clinical Benefit in Patients with Resected High-Risk StageⅢc/ⅣMelanoma[J].Clinical Cancer Research,2010,17(4):896-906.
[30]Friedman CF,Proverbs-Singh TA,Postow MA. Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors[J].JAMA Oncology,2016,2(10):1346-1353.
[31]Tirumani SH,Ramaiya NH,Keraliya A,et al. Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab[J]. Cancer Immunology Research,2015,3(10):1185-1192.
[32]Nishino M,Sholl LM,Hodi FS,et al. Anti-PD-1-related pneumonitis during cancer immunotherapy[J]. N Engl J Med,2015,373(3):286-288.
[33]Wang C,Yu X,Wang W. A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer[J]. Medicine(Baltimore),2016,95(52):e5539.
[34]Ciccarese C,Alfieri S,Santoni M,et al. New toxicity profile for novel immunotherapy agents:focus on immune-checkpoint inhibitors[J]. J Clin Oncol,2016,12(1):57-75.
[35]Gullo. Day-to-Day Variations of Serum Pancreatic Enzymes in Benign Pancreatic Hyperenzymemia[J]. Clin Gastroenterol Hepatol,2007,5(1):70-74.
[36]Alabed YZ,Aghayev A,Sakellis C,et al. Pancreatitis Secondary to Anti–Programmed Death Receptor 1 Immunotherapy Diagnosed by FDG PET/CT[J]. Clinical Nuclear Medicine,2015,40(11):528-529.
[37]Wilgenhof S,Neyns B,et al. Anti-CTLA-4 antibody-induced Guillain Barre syndrome in a melanoma patient[J]. Ann Oncol,2011,22(4):991-993.
[38]Morello S,Capone M,Sorrentino C,et al. Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab[J]. J Transl Med,2017,15(1):244.
[39]Kumar V,Chaudhary N,Garg M,et al. Current Diagnosis and Management of Immune Related Adverse Events(ir AEs)Induced by Immune Checkpoint Inhibitor Therapy[J]. Front Pharmacol,2017,8:49.
[40]Wilson MA,Guld K,Galetta S,et al. Acute visual loss after ipilimumab treatment for metastatic melanoma[J]. J Immunother Cancer,2016,4:66.
[41]Abdel-Wahab N,Shah M,Lopez-Olivo MA,et al. Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease:A Systematic Review[J]. Ann Intern Med,2018,168(2):121-130.
[42]Dan D,Tapparel L,Hugle T. Rheumatology. Checkpoint-induced autoimmunity-birth of a new disease[J]. Rev Med Suisse,2018,14(588):93-96.
[43]Ponisch W,Alten R,Baerwald C. Autoimmune reactions to immune checkpoint inhibitors[J]. Z Rheumatol,2017,76(2):57-62.
[44]Ott PA,Hodi FS,Kaufman HL,et al. Combination immunotherapy:a road map[J]. J Immunother Cancer,2017,5(1):1-16.
[45]Turajlic S,Gore M,Larkin J. First report of overall survival for ipilimumab plus nivolumab from the phaseⅢCheckmate 067 study in advanced melanoma[J]. Ann Oncol,2018,29(3),542-543.
[46]Callahan MK,Kluger H,Postow MA,et al. Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma:Updated Survival,Response,and Safety Data in a Phase I Dose-Escalation Study[J]. J Clin Oncol,2018,36(4):391-398.
[47]Wolchok JD,Chiarion-Sileni V,Gonzalez R,et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma[J]. N Engl J Med,2017,377(14):1345-1356.
[48]Sachpekidis C,Hassel JC,Dimitrakopoulou-Strauss A. Metastatic melanoma response to combination therapy with ipilimumab and vemurafenib[J]. Hell J Nucl Med,2017,20(3):251-253.
[49]Lyseng-Williamson,KA. Ipilimumab:a guide to its use in advanced melanoma in the EU[J]. Drugs Ther Perspect,2014,30(4):124-129.
[50]Chesney J,Imbert-Fernandez Y,Telang S,et al. Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors[J]. Melanoma Res,2018.
[51]Lang BM,Peveling-Oberhag A,Faidt D,et al. Long-term survival with modern therapeutic agents against metastatic melanoma-vemurafenib and ipilimumab in a daily life setting[J]. Med Oncol. 2018,35(3):24-35.
[52]Brzozowska M,Wierzba W,liwczyński A,et al. Analysis of survival of patients treated with vemurafenib,ipilimumab and dabrafenib for advanced skin melanoma in daily clinical practice(Real-World Data):retrospective analysis of patients treated under drug/reimbursement programmes in Poland in 2013~2016[J]. Melanoma Res,2018,28(1):52-55.
[53]Hoeller C,Michielin O,Ascierto PA,et al. Systematic review of the use of granulocyte-macrophage colony-stimulating factor in patients with advanced melanoma[J]. Cancer Immunol Immunother,2016,65(9):1015-1034.
[54]Kwek SS,Kahn J,Greaney SK,et al. GM-CSF and ipilimumab therapy in metastatic melanoma:Clinical outcomes and immunologic responses[J]. Oncoimmunology,2015,5(4):e1101204.
[55]van Dodewaard-de Jong JM,Santegoets SJ,van de Ven PM,et al. Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells[J]. Oncoimmunology,2015,5(4):e1105431.
[56]Dbritz J. GM-CSF and the role of myeloid regulatory cells in the pathogenesis and treatment of Crohn's disease[J]. Mol Cell Pediatr,2015,2(1):12-19.
[57]Chuang LS,Villaverde N,Hui KY,et al. A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF[J]. Gastroenterology,2016,151(4):710-723.