Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo

• Published in: Proceedings of the National Academy of Sciences - PNAS 2020-09, Vol.117 (37), p.22910-22919
• Main Authors: He, Xingkang, Yin, Xin, Wu, Jing, Wickström, Stina L., Duo, Yanhong, Du, Qiqiao, Qin, Shuhang, Yao, Shuzhong, Jing, Xu, Hosaka, Kayoko, Wu, Jieyu, Jensen, Lasse D., Lundqvist, Andreas, Salter, Alexander I., Bräutigam, Lars, Taoi, Wei, Chen, Yuguo, Kiessling, Rolf, Cao, Yihai
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antigens; Biological Sciences; Cancer; Cell Line, Tumor; Chimeric antigen receptors; Cytotoxicity, Immunologic - immunology; Fibroblasts; Immunotherapy; Immunotherapy - methods; Immunotherapy, Adoptive - methods; Lymphocyte Activation - physiology; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphoma; Malignancy; Medicin och hälsovetenskap; Melanoma; Metastases; Metastasis; Models, Animal; Neoplasm Metastasis - pathology; Neoplasms - metabolism; Precision medicine; Receptors, Antigen, T-Cell - immunology; Single-Cell Analysis - methods; T-Lymphocytes - immunology; Xenograft Model Antitumor Assays - methods; Zebrafish
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2009092117

Lymphocyte-based immunotherapy has emerged as a breakthrough in cancer therapy for both hematologic and solid malignancies. In a subpopulation of cancer patients, this powerful therapeutic modality converts malignancy to clinically manageable disease. However, the T cell- and chimeric antigen receptor T (CAR-T) cell-mediated antimetastatic activity, especially their impacts on microscopic metastatic lesions, has not yet been investigated. Here we report a living zebrafish model that allows us to visualize the metastatic cancer cell killing effect by tumor- infiltrating lymphocytes (TILs) and CAR-T cells in vivo at the single-cell level. In a freshly isolated primary human melanoma, specific TILs effectively eliminated metastatic cancer cells in the living body. This potent metastasis-eradicating effect was validated using a human lymphoma model with CAR-T cells. Furthermore, cancer-associated fibroblasts protected metastatic cancer cells from T cell-mediated killing. Our data provide an in vivo platform to validate antimetastatic effects by human T cell-mediated immunotherapy. This unique technology may serve as a precision medicine platform for assessing anticancer effects of cellular immunotherapy in vivo before administration to human cancer patients.