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T-helper 1 immunoreaction influences survival in muscle-invasive bladder cancer: proof of concept.

Ingels A, Sanchez Salas RE, Ravery V, Fromont-Hankard G, Validire P, Patard JJ, Pignot G, Prapotnich D, Olivier F, Galiano M, Barret E, Rozet F, Weber N, Cathelineau X - Ecancermedicalscience (2014)

Bottom Line: Survivors harboured higher lymphocytes densities versus non survivors (CD3: p = 0.0319; CD8: p = 0.0279).CD3 (p = 0.034) and CD8 (p = 0.034) lymphocytes densities were independently associated with cancer-specific survival on Cox model analyses.High CD3 and CD8 lymphocytes SR densities are associated with better cancer-specific survival for MIBC.

View Article: PubMed Central - PubMed

Affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.

ABSTRACT

Objective: To define immunoscore in bladder cancer studying T helper 1 (Th1) immunoreaction. To define a cancer-specific survival model based on Th1 cells infiltration.

Methods: A total of 252 patients underwent primary transurethral resection of bladder tumour at our Institution. A retrospective review of a selected cohort with pT1 and muscle-invasive bladder cancer (MIBC) lesions was performed. Pathology blocks were marked with CD3 and CD8 antibodies. Immune cells density in stromal reaction (SR) was measured on five distinct high-power field (HPF) by two dedicated uro-pathologist blinded for patients' evolution.

Statistics: Student test or non-parametric Wilcoxon test as appropriate to compare means between two groups. Receiver operating characteristics (ROC) curve to define markers threshold. Cox model to assess survival's predictors.

Results: Ten pT1 and 20 MIBC consecutive cases were analysed. Median follow-up was 33.4 months. Immunohistological analysis for pT1 lesions featured limited SR. For MIBC, the mean density of lymphocytes in the SR was of 105/HPF (CD3) and 86/HPF (CD8). Survivors harboured higher lymphocytes densities versus non survivors (CD3: p = 0.0319; CD8: p = 0.0279). CD3 (p = 0.034) and CD8 (p = 0.034) lymphocytes densities were independently associated with cancer-specific survival on Cox model analyses. The retrospective design and small size of cohorts are the study limitations.

Conclusions: High CD3 and CD8 lymphocytes SR densities are associated with better cancer-specific survival for MIBC. Th1 reaction against the tumour seems to be protective for bladder cancer. Further evaluation is warranted.

No MeSH data available.


Related in: MedlinePlus

Survival analysis in relation with CD8 cells infiltration. a. ROC curve of survival predicted by CD8 density. The Euclidean shortest distance link the graph top left to the ROC curve point corresponding to a cell density of 65 cells/HPF. b. Kaplan–Meier cancer-specific survival curve. After splitting the population between high and low CD8 density, around the 65 cells/HPF value, high infiltration appeared to be protective for cancer-specific death (p = 0.034).
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figure2: Survival analysis in relation with CD8 cells infiltration. a. ROC curve of survival predicted by CD8 density. The Euclidean shortest distance link the graph top left to the ROC curve point corresponding to a cell density of 65 cells/HPF. b. Kaplan–Meier cancer-specific survival curve. After splitting the population between high and low CD8 density, around the 65 cells/HPF value, high infiltration appeared to be protective for cancer-specific death (p = 0.034).

Mentions: There was a strong correlation between the mean densities of CD3 and CD8 cells (p = 0.0001) with a linear relation between these two data sets (p = 0.0001). There was a linear relation between the variable survival time from first TURBT and mean density of CD3 cells (p = 0.02) and CD8 cells (p = 0.0238). When we compared survivor versus non-survivor groups, mean densities of CD3 cells (p = 0.048) and CD8 cells (p = 0.028) were significantly different. The CD3 and CD8 areas under the ROC curves were respectively of 0.78 and 0.80 (Figure 2a). The cell densities thresholds to separate groups had been set at 97 cells/HPF (CD3) and 65 cells/HPF (CD8). Survival analysis showed significantly better survival among CD3- and CD8-infiltrated tumours (p = 0.047 and p = 0.034, respectively) (Figure 2b). Using Cox univariate analysis (Table 2), CD3 cells (p = 0.034) and CD8 cells (p = 0.034) were significant predictors of survival, low TILS density being associated with a cancer-specific mortality risk. None of the other variables analysed were significant on univariate analysis, probably because of the small set of data (grade was not tested since all the tumours were high-grade, T stage on CT scan p = 0.81, N stage on CT scan p = 0.88, age p = 0.87, body mass index p = 0.96, gender p = 0.27, treatment (cystectomy versus other treatments) p = 0.35). Thus there was no reason to perform a multivariate analysis.


T-helper 1 immunoreaction influences survival in muscle-invasive bladder cancer: proof of concept.

Ingels A, Sanchez Salas RE, Ravery V, Fromont-Hankard G, Validire P, Patard JJ, Pignot G, Prapotnich D, Olivier F, Galiano M, Barret E, Rozet F, Weber N, Cathelineau X - Ecancermedicalscience (2014)

Survival analysis in relation with CD8 cells infiltration. a. ROC curve of survival predicted by CD8 density. The Euclidean shortest distance link the graph top left to the ROC curve point corresponding to a cell density of 65 cells/HPF. b. Kaplan–Meier cancer-specific survival curve. After splitting the population between high and low CD8 density, around the 65 cells/HPF value, high infiltration appeared to be protective for cancer-specific death (p = 0.034).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263522&req=5

figure2: Survival analysis in relation with CD8 cells infiltration. a. ROC curve of survival predicted by CD8 density. The Euclidean shortest distance link the graph top left to the ROC curve point corresponding to a cell density of 65 cells/HPF. b. Kaplan–Meier cancer-specific survival curve. After splitting the population between high and low CD8 density, around the 65 cells/HPF value, high infiltration appeared to be protective for cancer-specific death (p = 0.034).
Mentions: There was a strong correlation between the mean densities of CD3 and CD8 cells (p = 0.0001) with a linear relation between these two data sets (p = 0.0001). There was a linear relation between the variable survival time from first TURBT and mean density of CD3 cells (p = 0.02) and CD8 cells (p = 0.0238). When we compared survivor versus non-survivor groups, mean densities of CD3 cells (p = 0.048) and CD8 cells (p = 0.028) were significantly different. The CD3 and CD8 areas under the ROC curves were respectively of 0.78 and 0.80 (Figure 2a). The cell densities thresholds to separate groups had been set at 97 cells/HPF (CD3) and 65 cells/HPF (CD8). Survival analysis showed significantly better survival among CD3- and CD8-infiltrated tumours (p = 0.047 and p = 0.034, respectively) (Figure 2b). Using Cox univariate analysis (Table 2), CD3 cells (p = 0.034) and CD8 cells (p = 0.034) were significant predictors of survival, low TILS density being associated with a cancer-specific mortality risk. None of the other variables analysed were significant on univariate analysis, probably because of the small set of data (grade was not tested since all the tumours were high-grade, T stage on CT scan p = 0.81, N stage on CT scan p = 0.88, age p = 0.87, body mass index p = 0.96, gender p = 0.27, treatment (cystectomy versus other treatments) p = 0.35). Thus there was no reason to perform a multivariate analysis.

Bottom Line: Survivors harboured higher lymphocytes densities versus non survivors (CD3: p = 0.0319; CD8: p = 0.0279).CD3 (p = 0.034) and CD8 (p = 0.034) lymphocytes densities were independently associated with cancer-specific survival on Cox model analyses.High CD3 and CD8 lymphocytes SR densities are associated with better cancer-specific survival for MIBC.

View Article: PubMed Central - PubMed

Affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.

ABSTRACT

Objective: To define immunoscore in bladder cancer studying T helper 1 (Th1) immunoreaction. To define a cancer-specific survival model based on Th1 cells infiltration.

Methods: A total of 252 patients underwent primary transurethral resection of bladder tumour at our Institution. A retrospective review of a selected cohort with pT1 and muscle-invasive bladder cancer (MIBC) lesions was performed. Pathology blocks were marked with CD3 and CD8 antibodies. Immune cells density in stromal reaction (SR) was measured on five distinct high-power field (HPF) by two dedicated uro-pathologist blinded for patients' evolution.

Statistics: Student test or non-parametric Wilcoxon test as appropriate to compare means between two groups. Receiver operating characteristics (ROC) curve to define markers threshold. Cox model to assess survival's predictors.

Results: Ten pT1 and 20 MIBC consecutive cases were analysed. Median follow-up was 33.4 months. Immunohistological analysis for pT1 lesions featured limited SR. For MIBC, the mean density of lymphocytes in the SR was of 105/HPF (CD3) and 86/HPF (CD8). Survivors harboured higher lymphocytes densities versus non survivors (CD3: p = 0.0319; CD8: p = 0.0279). CD3 (p = 0.034) and CD8 (p = 0.034) lymphocytes densities were independently associated with cancer-specific survival on Cox model analyses. The retrospective design and small size of cohorts are the study limitations.

Conclusions: High CD3 and CD8 lymphocytes SR densities are associated with better cancer-specific survival for MIBC. Th1 reaction against the tumour seems to be protective for bladder cancer. Further evaluation is warranted.

No MeSH data available.


Related in: MedlinePlus