PD-L1在膀胱癌组织中表达及对根治性膀胱切除术后患者预后影响
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摘要
目的探讨PD-L1在膀胱癌中表达及其对根治性膀胱切除术后患者预后的影响。方法选取自2010年12月至2013年1月于北部战区总医院行膀胱根治性切除术的61例患者的肿瘤组织及正常膀胱组织标本为研究对象。采用免疫组织化学方法对肿瘤组织及正常膀胱组织中PD-L1表达情况进行检测,并对患者预后进行随访,根据其临床结果统计分析无复发生存期、疾病特异生存期及总生存期。结果正常膀胱组织PD-L1阳性率为6.7%,明显低于肿瘤组织的45.1%(P<0.05)。膀胱癌肿瘤细胞上PD-L1表达对中位无复发生存期无影响(P>0.05),对肿瘤患者中位总生存期及中位疾病特异生存期有影响(P<0.05)。被肿瘤浸润的免疫细胞上的PD-L1表达对患者无复发生存期、疾病特异生存期及总生存期均无影响(P>0.05)。结论肿瘤细胞PD-L1表达与膀胱癌患者疾病特异生存期及总生存期相关,而与无复发生存期无关。肿瘤细胞上高PD-L1是肿瘤疾病特异生存期及总生存期负面预后标志,可能是肿瘤逃逸或者耐药机制之一。
Objective To investigate the expression of PD-L1 in bladder cancer and its effect on prognosis after radical cystectomy.Methods A retrospective study was performed on 61 cases of tumor tissues and normal bladder tissues which were cut from December 2010 to January 2013.The expression of PD-L1 in tumor tissues and normal bladder tissues was detected by immunohistochemistry,and the prognosis of the patients was followed up.According to the clinical results, the recurrence free survival,disease-specific survival and overall survival were statistically analyzed.Results The positive rate of PD-L1 in normal bladder tissues was 6.7%,which was significantly lower than that in tumor tissues(45.1%),and the difference was statistically significant(P<0.05).PD-L1 expression on bladder cancer tumor cells had no effect on the median recurrence-free survival(P>0.05),and had an effect on the median overall survival and the median disease-specific survival of tumor patients(P<0.05).The expression of PD-L1 on immune cells infiltrated by tumor has no effect on the recurrence free survival,disease-specific survival and overall survival of patients(P>0.05).Conclusion PD-L1 expression in tumor cells is correlated with disease-specific survival and overall survival of bladder cancer patients,while not with recurrence-free survival.High PD-L1 on tumor cells is a marker of tumor disease-specific survival and overall survival negative prognosis,which may be one of the mechanisms of tumor escape or drug resistance.
Objective To investigate the expression of PD-L1 in bladder cancer and its effect on prognosis after radical cystectomy.Methods A retrospective study was performed on 61 cases of tumor tissues and normal bladder tissues which were cut from December 2010 to January 2013.The expression of PD-L1 in tumor tissues and normal bladder tissues was detected by immunohistochemistry,and the prognosis of the patients was followed up.According to the clinical results, the recurrence free survival,disease-specific survival and overall survival were statistically analyzed.Results The positive rate of PD-L1 in normal bladder tissues was 6.7%,which was significantly lower than that in tumor tissues(45.1%),and the difference was statistically significant(P<0.05).PD-L1 expression on bladder cancer tumor cells had no effect on the median recurrence-free survival(P>0.05),and had an effect on the median overall survival and the median disease-specific survival of tumor patients(P<0.05).The expression of PD-L1 on immune cells infiltrated by tumor has no effect on the recurrence free survival,disease-specific survival and overall survival of patients(P>0.05).Conclusion PD-L1 expression in tumor cells is correlated with disease-specific survival and overall survival of bladder cancer patients,while not with recurrence-free survival.High PD-L1 on tumor cells is a marker of tumor disease-specific survival and overall survival negative prognosis,which may be one of the mechanisms of tumor escape or drug resistance.
引文
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[2] Herbst RS,Soria JC,Kowanetz M,et al.Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients[J].Nature,2014,515(7528):563-567.
[3] Bennett JM.Changes in the updated 2016:WHO classification of the myelodysplastic syndromes and related myeloid neoplasms[J].Clin Lymphoma Myeloma Leuk,2016,16(11):607-609.
[4] Rosenberg JE,Hoffman-Censits J,Powles T,et al.Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy:a single-arm,multicentre,phase 2 trial[J].Lancet,2016,387(10031):1909-1920.
[5] Stein JP,Lieskovsky G,Cote R,et al.Radical cystectomy in the treatment of invasive bladder cancer:long-term results in 1,054 patients[J].J Clin Oncol,2001,19(3):666-675.
[6] Morales A,Eidinger D,Bruce AW.Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors[J].J Urol,1976,116(2):180-183.
[7] Davarpanah NN,Yuno A,Trepel JB,et al.Immunotherapy:a new treatment paradigm in bladder cancer[J].Curr Opin Oncol,2017,29(3):1.
[8] Sharma P,Retz M,Siefker-Radtke A,et al.Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275):a multicentre,single-arm,phase 2 trial[J].Lancet Oncol,2017,18(3):312-322.
[9] Topalian SL,Drake CG,Pardoll DM.Immune checkpoint blockade:a common denominator approach to cancer therapy[J].Cancer Cell,2015,27(4):450-461.
[10] Wang X,Teng F,Kong L,et al.PD-L1 expression in human cancers and its association with clinical outcomes[J].Onco Targets Ther,2016,9:5023-5039.
[11] Postow MA,Callahan MK,Wolchok JD.Immune checkpoint blockade in cancer therapy[J].J Clin Oncol,2015,33(17):1974-1982.
[12] Mukherji D,Jabbour MN,Saroufim M,et al.Programmed death-ligand 1 expression in muscle-invasive bladder cancer cystectomy specimens and lymph node metastasis:a reliable treatment selection biomarker[J].Clin Genitourin Cancer,2016,14(2):183-187.
[13] Reck M,Rodriguez-Abreu D,Robinson AG,et al.Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer[J].N Engl J Med,2016,375(19):1823-1833.
[14] Nguyen KQ,Tsou WI,Calarese DA,et al.Overexpression of MERTK receptor tyrosine kinase in epithelial cancer cells drives efferocytosis in a gain-of-function capacity[J].J Biol Chem,2014,289(37):25737-25749.
[15] Erlmeier F,Seitz AK,Hatzichristodoulou G,et al.The role of PD-L1 expression and intratumoral lymphocytes in response to perioperative chemotherapy for urothelial carcinoma[J].Bladder Cancer,2016,2:425-432.
[16] Baras AS,Drake C,Liu JJ,et al.The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder[J].Oncoimmunology,2016,5:e1134412.