背景：目标针对T细胞免疫受体与免疫球蛋白和ITIM结构域（TIGIT）/CD155轴表明，恢复抗肿瘤免疫的潜力很大。然而，在大规模胰腺导管腺癌（PDAC）患者中，对其免疫表型和预后意义的研究仍然有限。方法：我们设计了三个七色多光谱面板，使用多重免疫组织化学方法，在272个PDAC样本中研究了TIGIT/CD155蛋白表达、免疫微环境特征、预后价值以及对辅助化疗的反应。结果：我们揭示了PDAC免疫微环境的低免疫原性和高异质性，其特征是丰富的CD3+ T细胞和CD68+巨噬细胞，以及激活的细胞毒性T淋巴细胞的低浸润。相比于癌旁组织，PDAC组织中TIGIT和CD155的表达较高。TIGIT表达的肿瘤浸润淋巴细胞与CD45RO+ T细胞的密度高度相关；TIGTI+CD8+ T细胞与CD3+CD45RO+FOXP3+的高浸润相关。CD155+CK+与CD3+以及CD3+CD8+CD45RO+ T细胞的密度显著相关。TCs中TIGIT的高阳性率、CD8+ T细胞中的TIGIT以及巨噬细胞中的CD155与无进展生存率和疾病特异性生存率差，而其临床意义与PD-L1状态相关。值得注意的是，PDAC患者中TIGIT+CK+或TIGIT+CD8+与CD155+CD68+的空间共存表示预后差且耐药于辅助化疗。结论：我们的研究结果表明，靶向TIGIT/CD155免疫抑制轴可能有助于患者分层和改善PDAC的临床结果。 （以上中文翻译仅供参考，并无法完全保证符合学术论文的格式和表达方式）

Background: Targeting emerging T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT)/CD155 axis shows promise for restoring anti-tumor immunity, but its immune phenotypes and prognostic significance in a large cohort of pancreatic ductal adenocarcinoma (PDAC) are limited. Methods: Three seven-color multispectral panels were rationally designed to investigate the protein expression, immune-microenvironmental feature, prognostic value, and the response to adjuvant chemotherapy of TIGIT/CD155 in 272 PDAC specimens using multiplex immunohistochemistry. Results: We revealed low immunogenicity and high heterogeneity of the PDAC immune microenvironment featured by abundant CD3+ T cells and CD68+ macrophages and low infiltration of activated cytotoxic T lymphocytes. TIGIT and CD155 were highly expressed in PDAC tissues compared to paracancerous tissues. Tumor-infiltrating lymphocytes expressing TIGIT were correlated with high densities of CD45RO+ T cells; TIGTI+CD8+ T cells were associated with high infiltration of CD3+CD45RO+FOXP3+. CD155+CK+ were significantly related to high densities of CD3+ and CD3+CD8+CD45RO+ T cells. High positive rates for TIGIT in TCs, CD8+ T cells, and CD155 in macrophages were correlated with poor progression-free and disease-specific survival, respectively, and their clinical significance was correlated with PD-L1 status. Notably, spatial co-existence of TIGIT+CK+ or TIGIT+CD8+ and CD155+CD68+ indicated poor survival and resistance to adjuvant chemotherapy response in patients with PDAC. Conclusion: Our findings suggest that targeting TIGIT/CD155 immunosuppressive axis may guide patient stratification and improve the clinical outcome of PDAC.© The author(s).