【研究方向】
肿瘤免疫细胞浸润减少是“冷肿瘤”形成的核心原因，也是制约免疫治疗疗效的关键因素。课题组致力于揭示这一过程背后的深层机制，并开发具有转化潜力的干预策略。
方向一：解析肿瘤内免疫细胞数量与功能失调机制。利用单细胞组学、空间转录组学和人源类器官模型等前沿技术，系统研究肿瘤微环境中免疫细胞的迁移、浸润及分化状态，揭示免疫细胞减少与功能失调如何协同推动“冷肿瘤”形成。
方向二：开发精准免疫干预策略。基于机制发现，团队积极探索多种靶向干预方法，包括小分子化合物筛选和抗体库构建，旨在增强抗肿瘤免疫细胞的迁移和浸润能力，重塑肿瘤免疫微环境，提升抗肿瘤免疫反应。
课题组迄今已在Immunity（IF 26.3）、Advanced Science（IF 14.1）、Nature communications（IF 17.5）、Cancer Immunology Research等期刊发表论文20余篇，其中部分成果被Nature和Science推荐为研究亮点。团队承担多项国家级及上海市科研项目，为课题组提供坚实的科研平台与资源。
Reduced immune cell infiltration is a major factor underlying the formation of “cold tumors” and a key limitation to the effectiveness of immunotherapy. Our group focuses on uncovering the mechanisms driving this process and developing intervention strategies with translational potential.
Research Direction 1: Mechanisms of immune cell infiltration and functional dysregulation in tumors
We employ cutting-edge approaches, including single-cell omics, spatial transcriptomics, and human organoid models, to systematically study the migration, infiltration, and differentiation of immune cells within the tumor microenvironment. We aim to reveal how decreases in immune cell numbers, together with functional impairments, contribute to the development of “cold tumors”.
Research Direction 2: Development of precision immunotherapeutic strategies
Building on these mechanistic insights, we are exploring various targeted interventions, including small-molecule screening and antibody library development, to enhance the migration and infiltration of anti-tumor immune cells, remodel the tumor immune microenvironment, and strengthen anti-tumor immune responses.
To date, our team has published over 20 papers in high-impact journals such as Immunity (IF 26.3), Advanced Science (IF 14.1), Nature Communications (IF 17.5), and Cancer Immunology Research, with several studies highlighted by Nature and Science. Our group also leads multiple national and Shanghai municipal research projects, providing a strong platform and resources to support these efforts.
【承担课题】
1. 国家自然科学基金面上项目，49万元，2025.01-2028.12
2. 国家自然科学基金面上项目，56万元，2022.01-2025.12
3. 国家自然科学基金青年项目，20万元，2018.01-2020.12
4. 上海市科委自然科学基金面上滚动项目，50万元，2024.12-2027.11
5. 上海市科委自然科学基金面上项目，20万元，2021.07- 2024.06
6. 上海市第十人民医院攀登人才计划，20万元，2021.01- 2022.12
7. 上海市第十人民医院国自然培育面上A类，10万元，2020.01-2021.12
【发表论文】
Zhang, Y#., Song, F.#, Yang, M., Chen, C., Cui, J., Xing, M., Dai, Y., Li, M., Cao, Y., Lu, L., et al. (2024). Gastrointestinal Dysmotility Predisposes to Colitis through Regulation of Gut Microbial Composition and Linoleic Acid Metabolism. Adv Sci (Weinh) 11, e2306297. 10.1002/advs.202306297. (IF 14.1)
Li, Y.#, Wang, S.#, Zhang, Y.#, Liu, Z., Zheng, Y., Zhang, K., Chen, S., Lv, X., Huang, M., Pan, X., et al. (2024). Ca(2+) transients on the T cell surface trigger rapid integrin activation in a timescale of seconds. Nat Commun 15, 6131. 10.1038/s41467-024-50464-0. (IF 17.5)
Song, F.#, Zhang, Y.#, Chen, Q.#, Bi, D., Yang, M., Lu, L., Li, M., Zhu, H., Liu, Y., and Wei, Q. (2023). Mast cells inhibit colorectal cancer development by inducing ER stress through secreting Cystatin C. Oncogene 42, 209-223. (IF 7.3)
Zhu, H.#, Bi, D.#, Zhang, Y.#, Kong, C.#, Du, J., Wu, X., Wei, Q., and Qin, H. (2022). Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations. Signal transduction and targeted therapy 7, 11. (IF 52.7)
Zhang, Y.#, Xie, R.#, Zhang, H.#, Zheng, Y., Lin, C., Yang, L., Huang, M., Li, M., Song, F., and Lu, L. (2021). Integrin β7 inhibits colorectal cancer pathogenesis via maintaining antitumor immunity. Cancer Immunology Research 9, 967-980. (IF 8.2)
Lin, C.#, Zhang, Y.#, Zhang, K., Zheng, Y., Lu, L., Chang, H., Yang, H., Yang, Y., Wan, Y., and Wang, S. (2019). Fever promotes T lymphocyte trafficking via a thermal sensory pathway involving heat shock protein 90 and α4 integrins. Immunity 50, 137-151. e136. (IF 26.3)
Guo, J.#, Zhang, Y.#, Li, H.#, Chu, H.#, Wang, Q., Jiang, S., Li, Y., Shen, H., Li, G., and Chen, J. (2018). Intramembrane ionic protein–lipid interaction regulates integrin structure and function. PLoS Biology 16, e2006525. (IF 7.2)
Zhang, Y.#, Pan, Y.#, Lin, C.#, Zheng, Y., Sun, H., Zhang, H., Wang, J., Yuan, M., Duan, T., and Du, Q. (2016). Bile acids evoke placental inflammation by activating Gpbar1/NF-κ B pathway in intrahepatic cholestasis of pregnancy. Journal of molecular cell biology 8, 530-541. (IF 5.9)
Du, Q.#, Pan, Y.#, Zhang, Y.#, Zhang, H., Zheng, Y., Lu, L., Wang, J., Duan, T., and Chen, J. (2014). Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation. BMC medical genomics 7, 1-11.
