Non-spatial and spatial heterogeneity revealed a suppressive immune feature of Siglec-15 in lung adenocarcinomas.
Non-spatial and spatial heterogeneity revealed a suppressive immune feature of Siglec-15 in lung adenocarcinomas.
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DOI：
10.1186/s12967-023-04489-6
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发表时间：
2023-09-06
影响因子：
7.4
通讯作者：
Yang, Lili
中科院分区：
文献类型：
--
作者：
Li, Baihui;Guo, Yan;Yi, Yeran;Huang, Ziqi;Ren, Yulin;Wang, Hao;Yang, Lili
唾液酸结合免疫球蛋白样凝集素-15（Siglec-15）是一种新型的免疫治疗候选物，在肺腺癌（LUAD）中值得深入研究。进行了基于多重荧光的免疫组织化学研究，以评估天津队列LUAD中Siglec-15的表达和肿瘤浸润免疫细胞，验证队列为新潮04和07。本研究揭示Siglec-15与CD 8 + T细胞和肿瘤相关巨噬细胞（TAM）浸润呈正相关，但CD 8 + T细胞大多浸润在基质区，而非肿瘤区。在空间上，PD-L1−细胞中的Siglec-15+肿瘤细胞周围的CD 8 + T细胞较少，PD-L1−/+细胞中的Siglec-15+肿瘤细胞周围的TAM较多。Siglec-15+ TAM浸润了更多的CD 8 + T细胞，并且比Siglec-15− TAM和Siglec-15+肿瘤细胞更接近CD 8 + T细胞。Siglec-15+ TAM比Siglec-15+肿瘤细胞浸润更多的T细胞，并且更接近T细胞。Siglec-15+肿瘤细胞或TAM逆转了CD 8 + T细胞的预后价值，并增强了TCD 4和TAM的预后价值。基于Siglec-15和CD 8A/CD 8 + T细胞的免疫分型显示，具有高CD 8A和Siglec-15表达的患者表现出免疫活化。CD 8A低表达/CD 8 + T细胞浸润和Siglec-15过表达的患者与免疫抑制信号和代谢相关通路的激活有关，并浸润更多的TAM。我们揭示了Siglec-15+肿瘤细胞和TAM之间与CD 8 + T细胞相关的独特特征，以及Siglec-15与LUAD中免疫抑制TIME之间的独特关系，这可能为抗Siglec-15治疗提供潜在价值。在线版本包含补充材料，可通过10.1186/s12967-023-04489-6获得。
Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has emerged as a novel immunotherapy candidate, which deserves a comprehensive investigation in lung adenocarcinoma (LUAD). Multiplex fluorescence‐based immunohistochemistry was conducted to assess Siglec-15 expression and tumor-infiltrating immune cells in LUAD from Tianjin cohort, with validation cohorts Xinchao 04 and 07. This study revealed that Siglec-15 was positively correlated with CD8+ T cells and tumor-associated macrophages (TAMs) infiltration, but CD8+ T cells were mostly infiltrated in the stroma area, not in the tumor area. Spatially, fewer CD8+ T cells surrounded Siglec-15+ tumor cells in PD-L1− cells, and more TAMs surrounded Siglec-15+ tumor cells in PD-L1−/+ cells. Siglec-15+ TAMs infiltrated with more CD8+ T cells, and were closer to CD8+ T cells than Siglec-15− TAMs and Siglec-15+ tumor cells. Siglec-15+ TAMs infiltrated with more Tregs and were closer to Tregs than Siglec-15+ tumor cells. Siglec-15+ tumor cells or TAMs reversed CD8+ T cells prognosis value, and enhanced the prognosis value of Tregs and TAMs. The immunotyping based on Siglec-15 and CD8A / CD8+ T cells revealed that patients with high CD8A and Siglec-15 expression exhibited immune activation. Patients with low CD8A expression / CD8+ T cells infiltration and Siglec-15 overexpression were related to the activation of immunosuppressive signature and metabolism-related pathway, and infiltrated with more TAMs. We revealed the distinct characteristics between Siglec-15+ tumor cells and TAMs in relation to CD8+ T cells, and a unique relationship between Siglec-15 and immunosuppressive TIME in LUAD, which may provide potential value for anti-Siglec-15 therapy. The online version contains supplementary material available at 10.1186/s12967-023-04489-6.
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影响因子：
82.9
作者：
Gao J;Ward JF;Pettaway CA;Shi LZ;Subudhi SK;Vence LM;Zhao H;Chen J;Chen H;Efstathiou E;Troncoso P;Allison JP;Logothetis CJ;Wistuba II;Sepulveda MA;Sun J;Wargo J;Blando J;Sharma P
通讯作者：
Sharma P
影响因子：
4.6
作者：
Bonneville R;Krook MA;Kautto EA;Miya J;Wing MR;Chen HZ;Reeser JW;Yu L;Roychowdhury S
通讯作者：
Roychowdhury S
影响因子：
16.8
作者：
Kim TK;Herbst RS;Chen L
通讯作者：
Chen L
Siglec-15 的 N-糖基化减少了其溶酶体依赖性降解并促进其转运至细胞膜
DOI：
10.1016/j.bbrc.2020.08.111
发表时间：
2020-11-26
影响因子：
3.1
作者：
Chen, Xiaojian;Dang, Xuening;Huang, Zhenyu
通讯作者：
Huang, Zhenyu
影响因子：
3
作者：
Deng M;Brägelmann J;Schultze JL;Perner S
通讯作者：
Perner S