肿瘤细胞治疗研究
英文原题：Presence, Subtypes, and Prognostic Significance of Tertiary Lymphoid Structures in Urothelial Carcinoma of the Bladder.
TLS 在 UCB 中具有异质性，且 TLS 和 GC 结构与 TIL 密度及预后事件相关。
目的：评估膀胱尿路上皮癌（UCB）中三级淋巴结构（TLS）的存在及亚型，并分析其相关临床病理特征和预后意义。方法：研究纳入580例接受手术治疗的UCB患者，包括非肌层浸润性膀胱癌（NMIBC）313例和肌层浸润性膀胱癌（MIBC）267例。通过CD20、CD3、Bcl-6及CD21免疫组化鉴定TLS及其亚型，并依据有无生发中心（GC）将TLS分为非GC型（nGC）和GC型。以无病生存期（DFS）为终点，评估TLS及其亚型的预后意义。结果：MIBC中TLS比NMIBC更常见（67.8%比48.2%，P<0.001），TIL（肿瘤浸润淋巴细胞）平均密度也显著更高（24.0%比17.5%，P<0.001）。UCB中TLS存在、GC结构形成与TIL浸润呈正相关。共191例患者发生终点事件；与发生事件者相比，无疾病进展患者TIL密度更高、TLS更多（P<0.05）。Kaplan-Meier曲线显示，TLS与NMIBC（P=0.041）和MIBC（P=0.049）患者更佳DFS相关，但Cox多变量分析未证实TLS具有预后意义。结论：UCB中的TLS具有异质性，TLS和GC结构与TIL密度及预后事件相关，但TLS作为预后指标的价值尚不明确，仍需进一步研究。
OBJECTIVE: To evaluate the presence and subtypes of tertiary lymphatic structures (TLSs) in urothelial carcinoma of the bladder (UCB) and to analyze their associated clinicopathological characteristics and prognostic significance. METHODS: The study enrolled 580 patients with surgically treated UCB, including 313 non-muscle invasive bladder cancer (NMIBC) and 267 muscle-invasive bladder cancer (MIBC). The presence and subtypes of TLSs were identified by immunohistochemistry (CD20, CD3, Bcl-6, and CD21). TLSs were classified into non-GC (nGC) TLS and GC TLS subtypes based on germinal center (GC) formation. Disease-free survival (DFS) was used as an endpoint outcome to evaluate the prognostic significance of TLS and its subtypes in UCB. RESULTS: TLSs were more common in MIBC than in NMIBC (67.8% vs 48.2%, P < .001), and the tumor-infiltrating lymphocyte (TIL) mean density was significantly higher in MIBC than in NMIBC (24.0% vs 17.5%, P < .001). Moreover, a positive correlation was found between TLS presence and GC structure formation and TIL infiltration in UCB. Endpoint events occurred in 191 patients. Compared to patients with endpoint events, patients without disease progression exhibited higher TIL density and more TLSs (P < .05). Kaplan-Meier curves showed that TLS was associated with better DFS in NMIBC (P = .041) and MIBC (P = .049). However, the Cox multivariate analysis did not demonstrate the prognostic significance of TLS. CONCLUSIONS: TLS is heterogeneous in UCB, and that TLS and GC structures are related to TIL density and prognostic events. However, TLS as a prognostic indicator remains unclear, warranting further investigation.
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