Attenuated immune surveillance during squamous cell transformation of pancreatic adenosquamous cancer defines new therapeutic opportunity for cancer interception

作者：Xinyuan Chen, Shanyue Sun, Shuofeng Li, Shuangni Yu, Jie Chen, Xianlong Chen · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2025-012066 · 被引用次数：5 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

Background Pancreatic adenosquamous cancer (PASC) is an extremely rare subtype of pancreatic cancer characterized by a poorer prognosis and higher likelihood of metastasis compared with the more prevalent pancreatic ductal adenocarcinoma (PDAC). Although genomic changes during PASC tumorigenesis have been documented, the corresponding alterations in the tumor immune microenvironment (TIME) remain inadequately elucidated. Therefore, this study aims to analyze the immune landscape of PASC by employing multiplex immunohistochemistry (mIHC) and digital image analysis. Methods In this study, we analyzed four independent cohorts comprising 120 patients with PASC and 386 patients with PDAC. We employed mIHC to quantify three in situ panels of immuno-oncology-related biomarkers at subcellular resolution. We then used five samples to perform laser capture microdissection, RNA sequencing, and whole-exome sequencing to explore the underlying mechanisms of the compartment-specific immune phenotypes in PASC. Results Our findings revealed a more immunosuppressive TIME in PASC compared with PDAC, characterized by a decreased abundance of T cells. Immune cell types indicative of enhanced immune surveillance, including cytotoxic and memory T cells and antigen-experienced T cells, were present at significantly lower densities in PASC compared with PDAC. Conversely, some immunosuppressive macrophage phenotypes exhibited increased distribution in PASC. Immunosuppressive immune cells (ICs) were a...