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Sources of Funding: CUA-Pfizer urology resident grant awarded to Alice Yu

Introduction

It is known that patients with the same TNM stage can have different clinical outcomes. There is increasing evidence that cytotoxic T lymphocytes distribution between the tumour core (CT) and invasive margin (IM) correlates with disease free survival (DFS) and overall survival (OS) in other malignancies. The effect of a particular immune response is determined by the balance between the various T-cell subtypes involved, mainly the cytotoxic lymphocytes CD8+ and CD3+. In this sense, the Immunoscore, a new approach to the classification of cancer using the number, type and distribution of immune cells has been developed. Our objective was to evaluate the the prognostic impact of lymphocyte distribution in bladder cancer.

Methods

Hematoxylin and eosin (H&E) stained slides of cystectomy permanent sections with tumour involvement and identifiable invasive margin were selected and stained for CD8+ lymphocytes. Three non-contiguous areas of highest lymphocyte density were selected from both CT and IM. The number of CD8+ lymphocytes were calculated using Aperio image analysis software. Nonparametric (Wilcoxon–Mann–Whitney) test was used to identify markers with a significantly different expression among patient groups. Kaplan–Meier curves were used to visualize differences between DFS and OS.

Results

67 patients who had cystectomy for T1-T4 bladder cancer were included in the study. High concentration of CD8+ lymphocytes in the tumour margin is associated with better DFS (P=0.005) and OS (P=0.03). Similar results were found for CD3+ lymphocytes with regards to DFS (P=0.05) but results did not meet statistical significance for OS (P=0.07). A higher Immunoscore is also associated with better DFS (P=0.04). After controlling for T stage, lymphovascular invasion, and peri-operative chemotherapy, higher levels of CD8+ in the invasive margin was independently associated with better outcomes (DFS: HR 0.26, 95% CI 0.10-0.68, P=0.006, OS: HR 0.031, 95% CI 0.10-0.97, P=0.04)

Conclusions

The host’s own immune system plays a valuable role in cancer progression. Our data suggests that a strong immune response against the tumour, as demonstrated by high concentration of CD8+ lymphocytes in the tumour margin, is independently associated with better prognosis. In the future, we plan on evaluating markers other than CD3+ that can be used with CD8+ for more accurate Immunoscore determination for bladder cancer.

Funding

CUA-Pfizer urology resident grant awarded to Alice Yu