Visualization of human T lymphocyte-mediated eradication of cancer cells in vivoShow others and affiliations
2020 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 117, no 37, p. 22910-22919Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
NATL ACAD SCIENCES , 2020. Vol. 117, no 37, p. 22910-22919
Keywords [en]
cancer; metastasis; lymphocyte; zebrafish; cancer therapy
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-171353DOI: 10.1073/pnas.2009092117ISI: 000580028100049PubMedID: 32859758OAI: oai:DiVA.org:liu-171353DiVA, id: diva2:1501009
Note
Funding Agencies|European Research Council (ERC) advanced grant ANGIOFATEuropean Research Council (ERC) [250021]; Swedish Research CouncilSwedish Research Council; Swedish Cancer Foundation; Swedish Childrens Cancer Foundation; Karolinska Institute FoundationKarolinska Institutet; Karolinska Institutes 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 FoundationNovo Nordisk Foundation; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW2015.0063]; Swedish Cancer SocietySwedish Cancer Society [CAN2016/315]; Cancer Society in Stockholm [164073]; Swedish Medical Research CouncilSwedish Medical Research Council (SMRC) [2016-01414]; Stockholm City Council [201700452]
2020-11-152020-11-152020-11-15