Abstract
4544 Background: Superficial transitional cell carcinoma (TCC) is an immune-responsive tumor evidenced by immunotherapy trials with BCG demonstrating improved survival. In contrast, more advanced muscle-invasive TCC is not considered an immunologically active tumor. Yet, host immune functions that may have a clinical impact on the biologic activity of these more invasive tumors have not been systemically evaluated. CD8+ T-cells are responsible for cytotoxicity and potential tumor eradication by interaction with antigen plus human leukocyte antigens (HLA). A clear association between intratumoral CD8+ T-cells and clinical outcome has not been established in TCC. Methods: We performed pathological, immunohistochemical and RT-PCR analyses of 69 TCC patient samples that were obtained with appropriate informed consent on an Institutional Review Board (IRB)-approved protocol. The samples were studied for pathological stage, tumor-associated antigen expression, class I HLA expression, and CD8+ intratumoral T-cells. Systemic CD8+ T-cells from one patient with positive CD8+ intratumoral T-cells were studied by tetramer analyses for reactivity against the NY-ESO-1 tumor antigen expressed on the patient’s tumor. Results: In a subset analysis, advanced TCC (pT2, pT3 and pT4) patients who had higher numbers of CD8+ tumor infiltrating lymphocytes (TILs) had a greater disease-free survival (p = 0.0002) and overall survival (p = 0.011) than similarly staged TCC patients with lower numbers of CD8+ TILs. In the multivariate analyses, CD8+ TILs (p = 0.04) and tumor stage (p < 0.001) were significant risk factors to predict overall survival. Furthermore, a CD8+ T-cell clone derived from one patient demonstrated strong recognition of the tumor antigen NY-ESO-1. Conclusions: This is the first report, to our knowledge, that CD8+ TILs is an important prognostic indicator for patients with advanced TCC. Investigational immunotherapy strategies to evoke CD8+ T-cell responses are warranted in patients with advanced TCC. [Table: see text]
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