Prediction of intravesical recurrence of non-muscle-invasive bladder cancer by evaluation of intratumoral Foxp3+ T cells in the primary transurethral resection of bladder tumor specimens

Ryosuke Murai, Yasushi Itoh, Susumu Kageyama, Misako Nakayama, Hirohito Ishigaki, Kazuo Teramoto, Mitsuhiro Narita, Tetsuya Yoshida, Keiji Tomita, Ken-ichi Kobayashi, Akinori Wada, Masayuki Nagasawa (+4 others)
2018 PLoS ONE  
Patients with a history of non-muscle-invasive bladder cancer sometimes have recurrence of tumors after transurethral resection of bladder tumor treatment. To find factors related to the recurrence of non-muscle-invasive bladder cancer, we examined tissue specimens taken at transurethral resection of bladder tumor as an initial treatment. We revealed the association between prognosis of non-muscle-invasive bladder cancer and infiltration of Foxp3 + T cells that suppress anti-tumor immunity in
more » ... tumor immunity in 115 primary non-muscle-invasive bladder cancer patients retrospectively identified and followed for at least 3 months after primary transurethral resection. In immunohistological staining, we counted the number of cells positive for CD3 and positive for CD3 and Foxp3 together and calculated the percentage of Foxp3 + T cells among the CD3 + T cells. The recurrence-free survival rate was calculated by the Kaplan-Meier method, and a Cox regression analysis of recurrence factors was performed. The median (interquartile range) percentage of Foxp3 + T cells in all cases was 17.1% (11.9, 11.4-23.3%). Compared by risk stratification, it was 11.4% (10.4, 7.8-18.2%) in the low-risk group (n = 32), 16.8% (12.6, 11.6-24.2%) in the intermediate-risk group (n = 45), and 22.0% (9.7, 16.4-26.1%) in the high-risk group (n = 38). The Kaplan-Meier survival analysis indicated that the Foxp3 + T cell high group (! 17.1%) had a worse RFS rate than did the low group (< 17.1%) (P = 0.006). In multivariate analysis, the percentage of Foxp3 + T cells was an independent risk factor for intravesical recurrence (hazard ratio 2.25). Thus, peritumoral Foxp3 + T cell infiltration was correlated to risk stratification and recurrence-free survival. Therefore, the percentage of Foxp3 + T cells in tumor specimens may predict a risk for intravesical recurrence. Relationship between Foxp3 + T cells and recurrence in non-muscle-invasive bladder cancer PLOS ONE | https://doi.0.114, log-rank test. (C) RFS rates after TURBT for intermediate-risk NMIBC patients with intravesical THP treatment. Black line: patients with low Foxp3 + cells (n = 15). Red line: patients with high Foxp3 + cells (n = 17). P = 0.537, log-rank test. (D) RFS rates after TURBT for high-risk NMIBC patients with intravesical BCG treatment. Black line: patients with low Foxp3 + cells (n = 10). Red line: patients with high Foxp3 + cells (n = 13). P = 0.070, log-rank test. https://doi.org/10.1371/journal.pone.0204745.g004 Relationship between Foxp3 + T cells and recurrence in non-muscle-invasive bladder cancer PLOS ONE | https://doi.
doi:10.1371/journal.pone.0204745 fatcat:t3jb4eo2sfhg3c6rplia7wjohu