CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Distinct immune cell infiltration patterns in pancreatic ductal adenocarcinoma (PDAC) exhibit divergent immune cell selection and immunosuppressive mechanisms.
Distinct immune cell infiltration patterns in pancreatic ductal adenocarcinoma (PDAC) exhibit divergent immune cell selection and immunosuppressive mechanisms.
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胰腺导管腺癌预后极差。对12例患者配对的肿瘤浸润CD45+细胞和外周血以及两个已发表数据集的单细胞多组学数据进行综合分析，揭示了复杂的免疫浸润格局。患者要么呈现髓系富集型，要么呈现适应性免疫富集型的肿瘤微环境。适应性免疫细胞富集与高度独特的B细胞和T细胞克隆选择、多样化和分化内在相关。利用TCR数据，我们在CD8效应记忆细胞、衰老细胞以及高度活化的调节性T细胞中观察到最大的克隆扩增，这些调节性T细胞在肿瘤内由初始细胞诱导产生。我们识别了可能导致抑制性微环境的通路，包括研究性靶点TIGIT/PVR和SIRPA/CD47。对APACT临床试验中患者的分析表明，髓系富集型患者的总生存期短于适应性细胞富集型患者。该疾病合理治疗开发策略包括增强B细胞反应、靶向免疫抑制性巨噬细胞以及特异性Treg细胞清除方法。
Pancreatic ductal adenocarcinoma has a dismal prognosis. A comprehensive analysis of single-cell multi-omic data from matched tumour-infiltrated CD45+ cells and peripheral blood in 12 patients, and two published datasets, reveals a complex immune infiltrate. Patients have either a myeloid-enriched or adaptive-enriched tumour microenvironment.
Adaptive immune cell-enriched is intrinsically linked with highly distinct B and T cell clonal selection, diversification, and differentiation. Using TCR data, we see the largest clonal expansions in CD8 effector memory, senescent cells, and highly activated regulatory T cells which are induced within the tumour from naïve cells.
We identify pathways that potentially lead to a suppressive microenvironment, including investigational targets TIGIT/PVR and SIRPA/CD47. Analysis of patients from the APACT clinical trial shows that myeloid enrichment had a shorter overall survival compared to those with adaptive cell enrichment. Strategies for rationale therapeutic development in this disease include boosting of B cell responses, targeting immunosuppressive macrophages, and specific Treg cell depletion approaches.
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