关于肺腺癌（LUAD），新兴的免疫治疗候选者——唾液酸结合免疫球蛋白样凝集素-15（Siglec-15）值得进行全面的研究。我们使用多重荧光免疫组织化学方法，对来自天津队列的LUAD标本进行了Siglec-15表达及肿瘤浸润免疫细胞的评估，通过Xinchao 04和07队列进行了验证。研究结果发现，Siglec-15与CD8+ T细胞和肿瘤相关巨噬细胞（TAMs）浸润呈正相关，但CD8+ T细胞主要浸润于间质区域，而非肿瘤区域。在PD-L1-细胞中，相对较少的CD8+ T细胞环绕Siglec-15+肿瘤细胞，而在PD-L1-/+细胞中，更多的TAMs环绕Siglec-15+肿瘤细胞。Siglec-15+ TAMs伴随着更多的CD8+ T细胞浸润，并且离CD8+ T细胞更近，相比之下，Siglec-15- TAMs和Siglec-15+肿瘤细胞与CD8+ T细胞的关系较少。Siglec-15+ TAMs伴随着更多的Treg细胞浸润，并且离Treg细胞更近，相比之下，Siglec-15+肿瘤细胞与Treg和TAMs的关系较少。Siglec-15+肿瘤细胞或TAMs扭转了CD8+ T细胞的预后价值，并增强了Treg和TAMs的预后价值。基于Siglec-15和CD8A/CD8+ T细胞的免疫分型揭示了高CD8A和Siglec-15表达的患者具有免疫激活特征。低CD8A表达/CD8+ T细胞浸润和Siglec-15过表达的患者与免疫抑制特征和与代谢有关的通路激活相关，并有更多TAMs浸润。我们揭示了Siglec-15+肿瘤细胞和TAMs与CD8+ T细胞之间的不同特征，以及Siglec-15与LUAD中免疫抑制肿瘤微环境之间的独特关系，这可能为抗Siglec-15治疗提供潜在价值。© 2023. BioMed Central Ltd., part of Springer Nature.

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.© 2023. BioMed Central Ltd., part of Springer Nature.