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Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy.

ABSTRACT: 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-1 than pT2 stage (p = 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, P = 0.036) in non-organ-confined disease, but with poorer OS (log-rank test, P = 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.

SUBMITTER: Zhang S

PROVIDER: S-EPMC5642242 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy.

Zhang Shiqiang S Wang Jun J Zhang Xinyu X Zhou Fangjian F

PeerJ 20171013

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 sta ...[more]

PMID: 29043112

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Project description:Bladder cancer (BCa) is the tenth most commonly diagnosed malignant cancer worldwide. Although adjuvant chemotherapy following radical cystectomy is a common therapy for muscle invasive bladder cancer patients, no applicable biomarkers exist to predict which patients will benefit from chemotherapy. In this study, we examined three immune cell markers, the chemokine CC motif ligand 2 (CCL2), the pan macrophage marker cluster of differentiation 68 (CD68) and the M2 macrophage marker cluster of differentiation 163 (CD163), using immunohistochemistry to determine their predictive value for the chemotherapy response in different nodal stage (pN0 vs. pN1 + 2) and tumor stage subgroups (pT2 vs. pT3 + 4). The prognosis was studied in terms of the overall survival (OS), disease-specific survival (DSS), and recurrence-free-survival (RFS) in 168 muscle invasive BCa patients. Chemotherapy was associated with a poorer prognosis in patients with a higher expression of the immune markers CCL2 (RFS), CD68 (DSS and RFS), and CD163 (DSS and RFS) in the N0 group and with poorer survival in patients with a higher expression of the immune markers CCL2 (OS, DSS, and RFS), CD68 (OS, DSS, and RFS), and CD163 (OS, DSS, and RFS) in the pT2 group when compared with treatments without chemotherapy. In contrast, chemotherapy was associated with a better prognosis in patients with a low expression of the immune markers CCL2 (DSS and RFS), CD68 (OS, DSS, and RFS), and CD163 (OS) in the N1 + 2 group. In addition, chemotherapy was associated with improved survival in patients with a low expression of the immune marker CD68 (OS and DSS) and there was a trend for a better prognosis in patients with a low expression of CD163 (OS) in the pT3 + 4 group compared to patients not treated with chemotherapy. Interestingly, CD68 appeared to be the most applicable immune marker to stratify patients by the outcome of chemotherapy in the nodal stage and tumor stage groups. Overall, we suggest that, in addition to the clinical factors of tumor stage and nodal stage, it is also meaningful to consider the abundance of immune cells, such as macrophages, to better predict the response to chemotherapy for BCa patients after radical treatment.

Dataset Information

Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy.

Publications

Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy.

Similar Datasets

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