CD3high and FoxP3- tumor-infiltrating lymphocytes in the invasive margin as a favorable prognostic marker in patients with invasive urothelial carcinoma of the bladder

Tumor-infiltrating lymphocytes (TILs) have been extensively explored as prognostic biomarkers and cellular immunotherapy methods in cancer patients. However, the prognostic significance of TILs in bladder cancer remains unresolved. We evaluated the prognostic effect of TILs in bladder cancer patients. Sixty-four bladder cancer patients who underwent surgical resection between 2018 and 2020 in Zhejiang Provincial People's Hospital were analyzed in this study. Immunohistochemistry was used to evaluate CD3, CD4, CD8, and FoxP3 expression on TILs in the invasive margin of tumor tissue, and the presence of TIL subsets was correlated with the disease-free survival (DFS) of bladder cancer patients. The relationship between clinical-pathological features and DFS were analyzed. A high level of CD3(+)TILs (CD3(high)TILs) (P = 0.027) or negative expression of FoxP3 TILs (FoxP3(-) TILs) (P = 0.016) was significantly related to better DFS in bladder cancer patients. Those with CD3(high)FoxP3(-) TILs had the best prognosis compared to those with CD3(high)FoxP3(+) TILs or CD3(low)FoxP3(-) TILs (P = 0.0035). Advanced age [HR 4.57, (1.86-11.25); P = 0.001], CD3(low) TILs [HR 0.21, (0.06-0.71); P = 0.012], CD8(low) TILs [HR 0.34, (0.12-0.94); P = 0.039], and FoxP3(+) TILs [HR 10.11 (1.96-52.27); P = 0.006] in the invasive margin were associated with a worse prognosis (DFS) by multivariate analysis. In conclusion, we demonstrated that CD3(high), FoxP3(-), and CD3(high)FoxP3(-) TILs in the invasive margin were significantly associated with better DFS. CD8(high) and CD4(high) TILs in the invasive margin tended to predict better DFS in bladder cancer. Patients with CD4(high)CD8(high) TILs in the invasive margin were likely to have a better prognosis.