Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 37, Pages 22910-22919Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2009092117
Keywords
cancer; metastasis; lymphocyte; zebrafish; cancer therapy
Categories
Funding
- European Research Council (ERC) advanced grant ANGIOFAT [250021]
- Swedish Research Council
- Swedish Cancer Foundation
- Swedish Children's Cancer Foundation
- Karolinska Institute Foundation
- Karolinska Institute's Distinguished Professor Award
- Torsten Soderberg Foundation
- Strategic Research Areas (SFO)-Stem Cell and Regeneration Medicine Foundation the Karolinska Institute
- Maud and Birger Gustavsson Foundation
- NOVO Nordisk Foundation
- Knut and Alice Wallenberg Foundation [KAW2015.0063]
- Swedish Cancer Society [CAN2016/315]
- Cancer Society in Stockholm [164073]
- Swedish Medical Research Council [2016-01414]
- Stockholm City Council [201700452]
- Swedish Research Council [2016-01414] Funding Source: Swedish Research Council
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Lymphocyte-based immunotherapy has emerged as a break-through 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.
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