Abstract
Background: Tertiary lymphoid structure (TLS) has been reported to be associated with prognosis and immunotherapy in certain cancers. In this study, we aimed to explore the prognostic role of TLS in Muscle-invasive bladder cancer (MIBC), and to analyze the clinicopathological and molecular factors affecting the formation of TLS.
Methods: Immunohistochemistry was used to detect the expression of TLS, CD8+ T cells, B cells, and plasma cells in 119 MIBC cases, of which 80 cases were tested by next generation sequencing (NGS) for analysising the differences in gene alterations between TLS-negative and TLS-positive.
Results:TLSs were present in 52.1% of MIBC cases. Patients with TLS had lower T and TNM stages, and had longer overall survival (OS) than patients without TLS. Multivariate analysis showed that TLS was an independent prognostic factor. The densities of B cells, CD8+ T cells, and plasma cells in tumors were significantly correlated with TLS, but in the cases with low density B cells, high density CD8+ T cells or high density plasma cells, differences in OS between the tumors with TLS and without TLS were not significant. Compared with TLS-negative tumors, TLS-positive tumors had lower frequency of TP53mutations and higher frequencies of FAT1, CDKN1A mutations. Tumor mutational burden (TMB)was not significantly different between the two groups, but was significantly associated with TLS in TP53 wild-type tumors.
Conclusions:TLS was an independent predictor of favorableprognosis in MIBC, and mainly played antitumor role effect through B cells. TP53mutations could inhibit the formation of TLS.