北京大学樊新元小组宣布他们揭示了深红色和超快光催化接近标记支持原位解剖肿瘤免疫相互作用的原发组织。这一研究成果发表在2025年3月4日出版的国际学术期刊《美国化学会杂志》上。

课题组介绍了CAT-Tissue，一种新颖的深红色光催化接近标记方法，可以超快速，高分辨率地分析原发组织中肿瘤免疫相互作用。通过利用纳米体-氯- e6作为光催化剂和生物素-苯胺作为探针，CAT-Tissue能够在共培养系统和原发肿瘤切片中快速全面地检测各种肿瘤-免疫相互作用。结合大量RNA测序，CAT-Tissue揭示了肿瘤邻近和肿瘤远端淋巴细胞之间不同的基因表达模式，突出了肿瘤邻近CD8⁺ T细胞的识别和免疫反应，表现出活化、效应和衰竭的表型。

通过利用具有优异组织穿透性和生物相容性的深红色光催化接近细胞标记策略，CAT-Tissue提供了一个具有高灵敏度和时空可控性的非遗传编码平台，用于快速分析复杂组织环境中的肿瘤-免疫相互作用，这可能会促进他们对肿瘤免疫学的理解，并指导开发更有效的免疫疗法。

据介绍，实体瘤的免疫治疗效果差异很大，受肿瘤微环境（TME）及其内肿瘤-免疫动态相互作用的影响。在对原生组织结构和微妙免疫反应干扰最小的情况下，原位解码这些相互作用对于理解肿瘤进展和优化治疗策略至关重要。

附：英文原文

Title: Deep-Red and Ultrafast Photocatalytic Proximity Labeling Empowered In Situ Dissection of Tumor-Immune Interactions in Primary Tissues

Author: Zhizheng Lou, Yan Zhang, Xuan Liang, Mengrui Cao, Yicong Ma, Peng R. Chen, Xinyuan Fan

Issue&Volume: March 4, 2025

Abstract: Immunotherapy efficacy in solid tumors varies greatly, influenced by the tumor microenvironment (TME) and the dynamic tumor-immune interactions within it. Decoding these interactions in situ with minimal interference with native tissue architecture and delicate immune responses is critical for understanding tumor progression and optimizing therapeutic strategies. Here, we introduce CAT-Tissue, a novel deep-red photocatalytic proximity labeling method that enables ultrafast, high-resolution profiling of tumor-immune interactions in primary tissues. By leveraging nanobody-Chlorin e6 as the photocatalyst and biotin-aniline as the probe, CAT-Tissue enabled the rapid and comprehensive detection of various tumor-immune interactions in both coculture systems and primary tumor sections. Coupled with bulk RNA-sequencing, CAT-Tissue revealed distinct gene expression patterns between tumor-neighboring and tumor-distal lymphocytes, highlighting the recognition and immune responses of tumor-neighboring CD8⁺ T cells, which exhibited activated, effector, and exhausted phenotypes. By leveraging a deep-red photocatalytic proximity cell labeling strategy with excellent tissue penetration and biocompatibility, CAT-Tissue offers a nongenetically encoded platform with high sensitivity and spatiotemporal controllability for rapid profiling tumor-immune interactions within complex tissue environments in situ, which may advance our understanding of tumor immunology and guide the development of more effective immunotherapies.

DOI: 10.1021/jacs.4c17879

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c17879