Impact of mature tertiary lymphoid structures on prognosis and therapeutic response of Epstein-Barr virus-associated gastric cancer patients.
Impact of mature tertiary lymphoid structures on prognosis and therapeutic response of Epstein-Barr virus-associated gastric cancer patients.
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DOI：
10.3389/fimmu.2022.973085
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
EB 病毒相关胃癌 (EBVaGC) 在富含免疫细胞的微环境中表现出独特的组织学特征，但三级淋巴结构 (TLS) 在 EBVaGC 中的作用尚未完全了解。我们从中国两个顶级癌症中心的 8517 例连续 GC 病例中回顾性鉴定出 EBVaGC。此外，我们评估了 TLS 在我们研究所的 148 名 EBVaGC 患者中的预后价值，然后在外部队列（76 名患者）中进行了验证。对 TLS 进行量化，并进一步分析其与总生存期 (OS) 和治疗反应的关系。多重免疫荧光染色和靶向测序分别用于表征 TLS 的组成和基因组景观。在我们的研究中，在训练组和验证组中，分别有 4.3% (190/4436) 和 2.6% (109/4081) 的 GC 出现 EBVaGC。在 EBVaGC 的肿瘤内 (94.6%) 和肿瘤周围 (77.0%) 组织中发现了 TLS，其中包含淋巴聚集体、初级和次级（即成熟的 TLS）滤泡。 Kaplan-Meier 分析表明，肿瘤内组织中成熟的 TLS 与训练和验证队列中良好的 OS 相关（p < 0.0001；p = 0.0108）。多变量分析表明，瘤内 TLS 成熟、pTNM 和 PD-L1 表达是 OS 的独立预后因素 (p < 0.05)。此外，成熟的 TLS 与 EBVaGC 患者的良好治疗反应显着相关。有趣的是，成熟 TLS 组中 SMARCA4 的突变频率显着较低。肿瘤内成熟的 TLS 与良好的预后和良好的治疗反应相关，表明它是一种潜在的预后生物标志物，并预测 EBVaGC 患者的良好治疗反应。
Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits unique histological characteristics within the immune-cell-rich microenvironment, but the role of tertiary lymphoid structure (TLS) in EBVaGC is not yet fully understood. We retrospectively identified EBVaGC from 8517 consecutive GC cases from the two top cancer centers in China. Furthermore, we evaluated the prognostic value of TLS in 148 EBVaGC patients from our institute and then validated it in an external cohort (76 patients). TLS was quantified and its relationships with overall survival (OS) and therapeutic response were further analyzed. Multiplex immunofluorescence staining and targeted sequencing were used to characterize the composition of TLS and the genomic landscape, respectively. In our study, EBVaGC was observed in 4.3% (190/4436) and 2.6% (109/4081) of GCs in the training and validation cohorts, respectively. TLS was identified in the intratumor (94.6%) and peritumor (77.0%) tissues with lymphoid aggregates, primary and secondary (i.e., mature TLSs) follicles in EBVaGC. Kaplan-Meier analysis showed that mature TLS in intratumoral tissues was associated with a favorable OS in the training and validation cohorts (p < 0.0001; p = 0.0108). Multivariate analyses demonstrated that intratumoral TLS maturation, pTNM, and PD-L1 expression were independent prognostic factors for OS (p < 0.05). Furthermore, the mature TLS was significantly associated with a good response to treatment in EBVaGC patients. Interestingly, the mutation frequency of SMARCA4 was significantly lower in the mature TLS groups. Intratumoral mature TLS was associated with a favorable prognosis and good therapeutic response, suggesting that it is a potential prognostic biomarker and predicts a good therapeutic response in EBVaGC patients.
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影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
通讯作者：
Wargo JA
影响因子：
4.1
作者：
Kohlruss, Meike;Grosser, Bianca;Keller, Gisela
通讯作者：
Keller, Gisela
影响因子：
64.8
作者：
Cabrita, Rita;Lauss, Martin;Jonsson, Goran
通讯作者：
Jonsson, Goran
影响因子：
25.7
作者：
Calderaro, Julien;Petitprez, Florent;Sautes-Fridman, Catherine
通讯作者：
Sautes-Fridman, Catherine
影响因子：
11.2
作者：
Gobert, Michael;Treilleux, Isabelle;Menetrier-Caux, Christine
通讯作者：
Menetrier-Caux, Christine