Chambuso Ramadhani, Meena Stephene S
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, United States.
Jiangzhong Cancer Research Center, Jiangxi University of Chinese Medicine, Nanchang, China.
J Natl Cancer Cent. 2024 Dec 6;5(1):3-7. doi: 10.1016/j.jncc.2024.12.002. eCollection 2025 Feb.
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) predisposition syndrome, characterized by a high mutational burden and microsatellite instability-high (MSI-H) tumors. Immunology of LS-associated CRC (LS-CRC) is unique, with significant implications for treatment. Despite well-established knowledge of LS immunology, immunotherapy dose and treatment response can vary significantly based on local tumor immunity and specific germline pathogenic variant of LS genes. This variability necessitates tailored surveillance strategies and new personalised immunotherapy approaches for LS patients. LS-CRC often benefits from immunotherapy due to the distinct tumor microenvironment (TME) and the variety of tumor infiltrating lymphocytes (TILs). This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images (WSIs) that accounts for the distinct TME of LS-CRC. By emphasizing the necessity of personalized medicine in hereditary cancer syndromes, the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.
林奇综合征（LS）是最常见的遗传性结直肠癌（CRC）易感综合征，其特征是具有高突变负荷和微卫星高度不稳定（MSI-H）肿瘤。LS相关结直肠癌（LS-CRC）的免疫学具有独特性，对治疗具有重要意义。尽管对LS免疫学已有充分了解，但免疫治疗剂量和治疗反应可能因局部肿瘤免疫和LS基因的特定种系致病变异而有显著差异。这种变异性使得有必要为LS患者制定量身定制的监测策略和新的个性化免疫治疗方法。由于独特的肿瘤微环境（TME）和多种肿瘤浸润淋巴细胞（TILs），LS-CRC通常受益于免疫治疗。本观点讨论了一种使用肿瘤全切片图像（WSIs）在单细胞水平分析空间TILs的新方法，该方法考虑了LS-CRC独特的TME。通过强调遗传性癌症综合征中个性化医疗的必要性，激发了通过精准肿瘤学改善患者预后的未来研究和临床实践。
