Open AccessProgrammed death ligand‐1 is associated with tumor infiltrating lymphocytes and poorer survival in urothelial cell carcinoma of the bladder
Author(s) -
Wang Bo,
Pan Wenwei,
Yang Meihua,
Yang Wenjuan,
He Wang,
Chen Xu,
Bi Junming,
Jiang Ning,
Huang Jian,
Lin Tianxin
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13887
Subject(s) - stromal cell , immune system , immunohistochemistry , pd l1 , bladder cancer , medicine , tumor infiltrating lymphocytes , cancer research , cystectomy , carcinoma , immunotherapy , pathology , cancer , immunology
Drugs blocking programmed death ligand‐1 ( PD ‐L1) have shown unprecedented activity in metastatic and unresectable bladder cancer. The purpose of the present study was to investigate the expression, clinical significance and association of PD ‐L1 with tumor‐infiltrating lymphocytes ( TIL ) in resectable urothelial cell carcinoma of the bladder ( UCB ). In this retrospective study, 248 UCB patients who received radical cystectomy or transurethral resection were examined. Immunohistochemistry was used to evaluate PD ‐L1 expression and stromal CD 8 + TIL , Th1 orientation T cell (T‐bet + ) and PD ‐1 + TIL densities within the intratumoral regions and associated stromal regions. Of the 248 specimens, 23% showed PD ‐L1 expression in tumor cells and 55% in tumor‐infiltrating immune cells. CD 8 + TIL , T‐bet + TIL and PD ‐1 + TIL were distributed throughout the tumor tissues and were more frequently distributed in stromal regions than in intratumoral regions. PD ‐L1 + tumor cells and PD ‐L1 + immune cells were positively associated with aggressive clinical features (all P < .05). Both PD ‐L1 + tumor cells and PD ‐L1 + immune cells were associated with poorer recurrence‐free and overall survival (all P < .05). Multivariate analysis showed that PD ‐L1 + immune cells were an independent prognostic factor for overall ( P = .001) and recurrence‐free survival ( P = .024). Notably, high stromal CD 8 + TIL and PD ‐1 + TIL density were associated with poorer overall survival ( P = .031 and P = .001, respectively). In the stroma, CD 8 + TIL density has strong positive association with PD ‐L1 + immune cells and PD ‐1 + TIL density (all P < .0001). These results suggested that an exhausted immune state occurred in the tumor stroma in UCB . Further clinical development of immune‐checkpoint inhibitors may be effective for resectable patients with UCB .