黑斑息肉综合征 (PJS) 是一种罕见的常染色体显性遗传病，其特征是各种癌症的风险升高。丝氨酸/苏氨酸激酶 11 (STK11) 基因是一种主要的肿瘤抑制基因，对于致瘤细胞内外的免疫逃避至关重要。它在肿瘤治疗领域越来越受到关注，特别是在免疫疗法开发的背景下。本研究旨在评估从生殖系 STK11 缺陷导致的 PJS 个体获得的息肉是否适合免疫疗法。此外，我们还试图确定 PJS 息肉和癌症之间与免疫逃避相关的潜在共同机制。为了实现这一目标，我们检查了 PJS 息肉以及家族性腺瘤性息肉病 (FAP) 和散发性息肉。息肉之间以及息肉与癌旁组织或结肠癌进行了比较。采用病理学和基因表达谱方法来表征浸润免疫细胞并评估免疫检查点基因的表达。我们的研究结果表明，PJS 息肉在免疫微环境方面比其他息肉表现出更接近癌症组织的相似性。值得注意的是，PJS 息肉表现出免疫检查点基因 CD80 的高表达和骨髓细胞的积累，特别是骨髓源性抑制细胞 (MDSC)。这些研究结果表明 PJS 患者癌症易感性增加的免疫生物学基础，为潜在的治疗潜力铺平了道路。免疫治疗在这一人群中的应用。此外，利用 PJS 作为模型可以促进免疫逃避机制的探索，使 PJS 和癌症患者受益。© 2024 作者。 《联合欧洲胃肠病学杂志》由 Wiley periodicals LLC 代表联合欧洲胃肠病学出版。

Peutz-Jeghers syndrome (PJS), is a rare autosomal dominant hereditary disease characterized by an elevated risk of various cancers. Serine/Threonine Kinase 11 (STK11) gene is a major tumor suppressor crucial for immune evasion with and beyond tumorigenic cells. It has garnered increasing attention in the realm of oncology treatment, particularly in the context of immunotherapy development.This study aimed to assess the suitability of polyps obtained from individuals with PJS, resulting from germline STK11 deficiency, for immunotherapy. Additionally, we seek to identify potential shared mechanisms related to immune evasion between PJS polyps and cancers. To achieve this, we examined PJS polyps alongside familial adenomatous polyposis (FAP) and sporadic polyps.Polyps were compared among themselves and with either the paracancerous tissues or colon cancers. Pathological and gene expression profiling approaches were employed to characterize infiltrating immune cells and assess the expression of immune checkpoint genes.Our findings revealed that PJS polyps exhibited a closer resemblance to cancer tissues than other polyps in terms of their immune microenvironment. Notably, PJS polyps displayed heightened expression of the immune checkpoint gene CD80 and an accumulation of myeloid cells, particularly myeloid-derived suppressor cells (MDSCs).The findings suggest an immunobiological foundation for the increased cancer susceptibility in PJS patients, paving the way for potential immune therapy applications in this population. Furthermore, utilizing PJS as a model may facilitate the exploration of immune evasion mechanisms, benefiting both PJS and cancer patients.© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.