CD103+ Tumor Infiltrating Lymphocytes Predict a Favorable Prognosis in Urothelial Cell Carcinoma of the Bladder.
OBJECTIVE
CD8(+) TILs at different tumor sites have diverse clinical attributes, which might result from distinct tumor microenvironments that promote differentiation into distinct subsets. However, only a few markers have been identified that can define CD8(+) T-cell subsets. CD103 is a marker of tissue resident memory CD8(+) T cells. In this retrospective study we investigated the cellular source and clinical significance of CD103 expression in urothelial cell carcinoma of bladder tissues in situ.


METHODS
Immunohistochemistry and immunofluorescence were used to identify the cellular source of CD103 in bladder urothelial cell carcinoma tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall and recurrence-free survival in 302 patients with bladder urothelial cell carcinoma.


RESULTS
CD8(+) T cells but not natural killer cells accounted for most CD103 expressing cells in bladder urothelial cell carcinoma tissues. Notably CD103(+) cells were predominantly located in intratumor regions rather than in associated stroma (p < 0.0001). The density of intratumor CD103(+) TILs was inversely associated with tumor size (p < 0.0001) and could represent a favorable prognostic predictor of overall and recurrence-free survival (p = 0.002 and 0.011, respectively). Moreover, intratumor CD103(+) TILs were positively associated with the expression of cognate ligand E-cadherin in intratumor regions of bladder urothelial cell carcinoma tissues (p = 0.008).


CONCLUSIONS
Our findings suggest that CD8(+) T cells might have a significant role in tumor immunity by expressing CD103 in intratumor regions of bladder urothelial cell carcinoma tissues. Intratumor CD103(+) TILs could potentially serve as a prognostic marker in patients with bladder urothelial cell carcinoma.
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Bo
B
Wang
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Shaoxu
S
Wu
Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Hong
H
Zeng
Department of Urology, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Zhuowei
Z
Liu
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Wen
W
Dong
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Wang
W
He
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Xu
X
Chen
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Xiaoliang
X
Dong
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Limin
L
Zheng
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China. Electronic address: tianxinl@sina.com.
Tianxin
T
Lin
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China. Electronic address: urolhj@sina.com.
Jian
J
Huang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002681:China / Q000453:epidemiology; D018572:Disease-Free Survival; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000276:immunology* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D001743:Urinary Bladder / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D039001:Integrin alpha Chains; C091367:alpha E integrins
CD8; antigens; carcinoma; lymphocytes; prognosis; tumor infiltrating; urinary bladder