Zhang Shiqiang, Wang Jun, Zhang Xinyu, Zhou Fangjian
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
PeerJ. 2017 Oct 13;5:e3921. doi: 10.7717/peerj.3921. eCollection 2017.
Tumor-infiltrating lymphocytes (TILs) are associated with better clinical outcomes in many tumors. TILs represent a cell-mediated immune response against the carcinoma. CD8+ TILs are a crucial component of cell-mediated immunity. The significance of CD8+ TILs has not been reported respectively in organ- and non-organ-confined urothelial carcinoma (UC) of the bladder. We explored the prognostic value of CD8+ TILs in the two groups. The presence of CD8+ TILs was assessed by immunohistochemical staining of whole tissue sections from 75 organ and 51 non-organ-confined disease patients with long-term follow-up, and its correlation with clinicopathological features and overall survival (OS) was determined. The CD8+ TIL immunohistochemical staining score was 0 (<1%), 1 (≥1%), 2 (≥5%), or 3 (≥10%) based on the percentage of positively stained cells out of total cells. A patient was considered CD8 negative if the score was 0. There were no associations between CD8+ TILs and age, sex, nuclear grade, and adjuvant or neoadjuvant chemotherapy in organ- and non-organ-confined disease. The presence of CD8+ TILs was seen more frequently in pTa- than pT stage ( = 0.033) in organ-confined disease. No associations between CD8+ TILs and pT stage, pN stage were found in non-organ-confined disease. CD8+ TILs were associated with better OS (log-rank test, = 0.036) in non-organ-confined disease, but with poorer OS (log-rank test, = 0.040) in organ-confined disease by the Kaplan-Meier method. In multivariate analysis, CD8+ TILs were an independent favorable prognostic factor in non-organ-confined disease, but were an independent unfavorable prognostic factor in organ-confined disease. These results suggest that CD8+ TILs have clinically significant anti-tumor activity in non-organ-confined disease, but may have pro-tumor activity in organ-confined disease. Therefore, we should be cautious if CD8+ TILs are aimed to be exploited in the treatment of bladder cancer.
肿瘤浸润淋巴细胞(TILs)与许多肿瘤更好的临床预后相关。TILs代表针对癌的细胞介导免疫反应。CD8⁺ TILs是细胞介导免疫的关键组成部分。CD8⁺ TILs在膀胱器官局限性和非器官局限性尿路上皮癌(UC)中的意义尚未分别报道。我们探讨了CD8⁺ TILs在这两组中的预后价值。通过对75例器官局限性和51例非器官局限性疾病患者的全组织切片进行免疫组织化学染色来评估CD8⁺ TILs的存在情况,并对其进行长期随访,确定其与临床病理特征及总生存期(OS)的相关性。根据阳性染色细胞占总细胞的百分比,CD8⁺ TIL免疫组织化学染色评分为0(<1%)、1(≥1%)、2(≥5%)或3(≥10%)。如果评分为0,则患者被认为CD8阴性。在器官局限性和非器官局限性疾病中,CD8⁺ TILs与年龄、性别、核分级以及辅助或新辅助化疗之间均无关联。在器官局限性疾病中,pTa期比pT期更频繁地出现CD8⁺ TILs(P = 0.033)。在非器官局限性疾病中,未发现CD8⁺ TILs与pT期、pN期之间存在关联。通过Kaplan-Meier法,在非器官局限性疾病中,CD8⁺ TILs与更好的OS相关(对数秩检验,P = 0.036),但在器官局限性疾病中与较差的OS相关(对数秩检验,P = 0.040)。在多变量分析中,CD8⁺ TILs在非器官局限性疾病中是独立的有利预后因素,但在器官局限性疾病中是独立的不利预后因素。这些结果表明,CD8⁺ TILs在非器官局限性疾病中具有临床上显著的抗肿瘤活性,但在器官局限性疾病中可能具有促肿瘤活性。因此,如果旨在将CD8⁺ TILs用于膀胱癌治疗,我们应谨慎行事。
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