scholarly journals Prognostic impact of tumor infiltrating lymphocytes in bladder urothelial carcinoma

2019 ◽  
Vol 8 (S3) ◽  
pp. S291-S292
Author(s):  
Hyung Suk Kim ◽  
Ja Hyeon Ku
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Bladder Urothelial Carcinoma ◽  
Infiltrating Lymphocytes

scholarly journals Prognostic Impact of APOBEC3B Expression in Metastatic Urothelial Carcinoma and Its Association with Tumor-Infiltrating Cytotoxic T Cells

2021 ◽  
Vol 28 (3) ◽  
pp. 1652-1662
Author(s):  
Hyunho Kim ◽  
Okran Kim ◽  
Myung Ah Lee ◽  
Ji Youl Lee ◽  
Sung-Hoo Hong ◽  
...  
Keyword(s):  
T Cells ◽  
Confidence Interval ◽  
Urothelial Carcinoma ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
Infiltrating Lymphocytes

APOBEC3B enzymes are endogenous carcinogenic mutagens. Metastatic urothelial carcinomas often harbor APOBEC3B-mediated mutations in which tCw to T or G substitution occurs. Here, we evaluated patient survival and CD8+ T-cell density according to APOBEC3B expression in patients with metastatic urothelial carcinoma who underwent cytotoxic chemotherapy. We performed a retrospective study on 94 patients with urothelial carcinoma who were treated with first line palliative chemotherapy. APOBEC3B expression and CD8+/CD3+ ratio of tumor-infiltrating lymphocytes were evaluated using immunohistochemistry. Kaplan–Meier survival curves were generated and the log-rank test was employed. The association between APOBEC3B expression and tumor-infiltrating lymphocytes was analyzed using Pearson’s chi-squared test. High APOBEC3B expression was detected in 71 of the 94 patients (75.5%). The median overall survival was longer in patients with high APOBEC3B expression (15 months) than in those with low expression (p = 0.045). The hazard ratio obtained based on the Cox regression analysis was 0.292 (95% confidence interval 0.118–0.723, p = 0.008). APOBEC3B expression was associated with the CD8+/CD3+ ratio (2.914, 95% confidence interval 1.030–8.249, p = 0.039). Collectively, APOBEC3B expression was an independent prognostic factor in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy. Tumor-infiltrating cytotoxic T cells were associated with APOBEC3B expression.

The prognostic role of tumor-infiltrating lymphocytes in urothelial carcinoma of bladder: A systematic review and meta-analysis

2020 ◽  
Author(s):  
Zhiqiang Yang ◽  
Yujin Bai ◽  
Xu Hu ◽  
Ping Han
Keyword(s):  
Systematic Review ◽  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Cochrane Library ◽  
Prognostic Impact ◽  
Infiltrating Lymphocytes ◽  
Urothelial Carcinoma Of Bladder

Abstract Background: Tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment are associated with different prognosis in various malignancies. However, their prognostic impact remains controversial in urothelial carcinoma of bladder (UCB). In this systematic review and meta-analysis, we aimed to investigate the prognostic value of TILs in UCB patients.Methods: A systematic review and meta-analysis was performed using Pubmed, Embase and Cochrane Library. Studies were eligible if they investigated the prognostic value of CD3+, CD4+, CD8+, Foxp3+ lymphocytes or TILs in UCB patients, by time-to-event survival analysis. All studies were appraised for risk of bias using the Quality and Prognosis Studies (QUIPS) criteria. Hazard rations (HRs) with their 95% confidence interval (CIs) from each study were used to generate pooled HRs. Results: A total of 14 studies assessing the impact of TILs on prognostic outcomes in UCB patients were included in final analysis. The pooled analysis indicated a favorable role of CD3+ TILs (HR 0.74 (95% CI 0.62-0.88) for overall survival) and CD8+ TILs (HR 0.46 (95% CI 0.28-0.74) for OS) in the clinical outcomes of UCB, while Foxp3+ TILs were associated with worse survival (HR 2.21 (95% CI 1.47-3.32) for recurrence-free survival). Conclusions: This systematic review and meta-analysis confirmed the favorable prognostic impact of CD3+ and CD8+ tumor-infiltrating T cells in UCB patients and found the association between Foxp3+ TILs and worse survival. Future studies using large cohorts and standardized methodology with regard to tumor subsites, stages and treatment modalities are needed to incorporate TILs with clinical practice.

Prognostic impact of tumor-infiltrating lymphocytes in non-small cell lung carcinomas

2021 ◽  
pp. 021849232110421
Author(s):  
Mona Mlika ◽  
Ayoub Saidi ◽  
Nesrine Mejri ◽  
Mehdi Abdennadher ◽  
Chokri Haddouchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Lung Carcinomas ◽  
Forkhead Box ◽  
Infiltrating Lymphocytes

Introduction Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. Methods We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. Results Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection ( p = 0.009), and a CD8/CD4 ratio ( p = 0.008) were prognostic factors for overall survival. Complete surgical resection ( p = 0.003), the forkhead box protein P3/CD8 ( p = 0.005), and forkhead box protein P3/CD4 ( p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate ( p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype ( p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age ( p = 0.004) and a CD8/CD4 ratio ( p = 0.016) were independent predictors of overall survival. Conclusion Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.

scholarly journals Clinical Impact of Tumor-Infiltrating Lymphocytes and PD-L1-Positive Cells as Prognostic and Predictive Biomarkers in Urological Malignancies and Retroperitoneal Sarcoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3153
Author(s):  
Makito Miyake ◽  
Shunta Hori ◽  
Takuya Owari ◽  
Yuki Oda ◽  
Yoshihiro Tatsumi ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Tumor Infiltrating Lymphocytes ◽  
Retroperitoneal Sarcoma ◽  
Prognostic Impact ◽  
Lymphocyte Migration ◽  
Primary Tumors ◽  
Urological Malignancies ◽  
Infiltrating Lymphocytes ◽  
Shed Light

Over the past decade, an “immunotherapy tsunami”, more specifically that involving immune checkpoint inhibitors (ICIs), has overtaken the oncological field. The interaction and cross-talk among tumor cells and several immune cells in the tumor microenvironment are dynamic and complex processes. As immune contexture can vary widely across different types of primary tumors and tumor microenvironments, there is still a significant lack of clinically available definitive biomarkers to predict patient response to ICIs, especially in urogenital malignancies. An increasing body of evidence evaluating urological malignancies has proven that tumor-infiltrating lymphocytes (TILs) are a double-edged sword in cancer. There is an urgent need to shed light on the functional heterogeneity in the tumor-infiltrating immune system and to explore its prognostic impact following surgery and other treatments. Notably, we emphasized the difference in the immunological profile among urothelial carcinomas arising from different primary origins, the bladder, renal pelvis, and ureter. Significant differences in the density of FOXP3-positive TILs, CD204-positive tumor-infiltrating macrophages, PD-L1-positive cells, and colony-stimulating factors were observed. This review discusses two topics: (i) the prognostic impact of TILs and (ii) predictive biomarkers for ICIs, to shed light on lymphocyte migration in four solid tumors, the urothelial carcinoma, renal cell carcinoma, prostate cancer, and retroperitoneal sarcoma.

Prognostic value of PD-1 and PD-L1 expression in patients with high-grade urothelial carcinoma of the upper urinary tract.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 358-358
Author(s):  
Laura-Maria Krabbe ◽  
Barbara Heitplatz ◽  
Ryan C Hutchinson ◽  
Solomon L Woldu ◽  
Sina Preuss ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Tumor Stage ◽  
Survival Outcomes ◽  
High Grade ◽  
Cancer Specific Survival ◽  
Infiltrating Lymphocytes

358 Background: To investigate the prognostic value of PD-1 and PD-L1 expression in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods: Tissue microarrays were created using 448 patients from the International UTUC collaboration who underwent extirpative surgery for high-grade UTUC and stained for PD-1 (antibody (AB): NAT105, diluted 1:250 from Ventana) and PD-L1 (AB: E1L3N prediluted from Cell Signaling). PD-1 and PD-L1 expression was assessed in a semi-quantitative fashion and any percentage of staining of the tumor cells (PD-L1) and tumor-infiltrating lymphocytes (PD-1) was considered positive. Univariate (UVA) and multivariate analyses (MVA) were performed to assess independent prognosticators of oncological outcomes. No funding was received. Results: Median age of the cohort was 69.2 years and 56.5% of patients were male. PD-L1 and PD-1 were positive in 24.1% and 37.5% of patients. PD-L1 positivity was associated with favorable pathological stage, where as PD-1 positivity was significantly associated with pelvicalyceal location, lymph node metastases, non-organ confined disease, presence of lymphovascular invasion, sessile architecture, necrosis, concomitant CIS, and history of non-muscle invasive bladder cancer. PD-L1 positivity was not significantly associated with survival outcomes. In Cox regression UVA, PD-1 positivity was associated with worse recurrence-free survival (RFS) (HR 1.5 (95%CI 1.08-2.14, p=0.016)), cancer-specific survival (CSS) (HR 1.5 (95%CI 1.07-2.19, p=0.021)), and overall survival (OS) (HR 1.5 (95%CI 1.10-1.97, p=0.009)). However in MVA, PD-1 positivity was not found to be an independent predictor of RFS, CSS or OS. Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and was a significant prognosticator for RFS, CSS and OS on UVA in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort. In MVA, the independent prognostic value of PD-1 was not confirmed. PD-L1 positivity was associated with lower tumor stage, but not with other pathological characteristics or survival outcomes.

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