Analysis of the Effector Functions of Vδ2 γδ T Cells and NK Cells against Cholangiocarcinoma Cells

Inthuon Kulma; Kesara Na-Bangchang; Andrea Carvallo Herrera; Ifeanyi Theodora Ndubuisi; Masashi Iwasaki; Hiromi Tomono; Craig T. Morita; Haruki Okamura; Hiroshi Mukae; Yoshimasa Tanaka

doi:10.3390/cells13161322

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Analysis of the Effector Functions of Vδ2 γδ T Cells and NK Cells against Cholangiocarcinoma Cells

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Analysis of the Effector Functions of Vδ2 γδ T Cells and NK Cells against Cholangiocarcinoma Cells

Inthuon Kulma, Kesara Na-Bangchang, Andrea Carvallo Herrera, Ifeanyi Theodora Ndubuisi, Masashi Iwasaki, Hiromi Tomono, Craig T. Morita, Haruki Okamura, Hiroshi Mukae and Yoshimasa Tanaka

Cells (Basel, Switzerland), Vol.13(16), 1322

08/08/2024

DOI: 10.3390/cells13161322

PMCID: PMC11352430

PMID: 39195212

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Abstract

Cholangiocarcinoma (CCA) is a rare disease characterized by malignant cells derived from the epithelial cells of the biliary duct system. Despite extensive treatments, the prognosis for CCA remains poor, emphasizing the critical need for the development of novel treatments. Considerable attention has been directed towards innate immune effector cells, which can recognize tumor cells independently of the major histocompatibility complex, laying the foundation for the development of off-the-shelf drugs. In this study, we cultured innate immune cells obtained from the peripheral blood of healthy adults and conducted a comparative analysis of the effector functions against CCA cell lines by Vδ2 γδ T cells and NK cells. This analysis was performed using standard short- and long-term cytotoxicity assays, as well as ELISA for IFN-γ. Vδ2 γδ T cells demonstrated cytotoxicity and IFN-γ production in response to CCA cells in a TCR-dependent manner, particularly in the presence of tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate, a bisphosphonate prodrug. In contrast, direct killing and antibody-dependent cellular cytotoxicity were relatively slow and weak. Conversely, NK cells displayed potent, direct cytotoxicity against CCA cells. In summary, both Vδ2 γδ T cells and NK cells show promise as innate immune effector cells for adoptive transfer therapy in the context of CCA.

bisphosphonate

cancer immunotherapy

cholangiocarcinoma

gamma delta T cell

interleukin-18

natural killer cell

Details

Title: Subtitle: Analysis of the Effector Functions of Vδ2 γδ T Cells and NK Cells against Cholangiocarcinoma Cells
Creators: Inthuon Kulma - Nagasaki University
Kesara Na-Bangchang - Thammasat University
Andrea Carvallo Herrera - Nagasaki University
Ifeanyi Theodora Ndubuisi - Nagasaki University
Masashi Iwasaki - Kyoto University
Hiromi Tomono - Nagasaki University
Craig T. Morita - University of Iowa
Haruki Okamura - Hyogo Medical University
Hiroshi Mukae - Nagasaki University
Yoshimasa Tanaka - Nagasaki University
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.13(16), 1322
Publisher: MDPI
DOI: 10.3390/cells13161322
PMID: 39195212
PMCID: PMC11352430
ISSN: 2073-4409
eISSN: 2073-4409
Grant note: Japan Science and Technology Agency (JST): JPMJST2281 Japan Science and Technology Agency (JST) START University Ecosystem Promotion Type: 16K08844, 23K06677, JP223fa627004 Ministry of Education, Culture, Sports, Science and Technology (MEXT): A48, A90 Japan Agency for Medical Research and Development (AMED): 23ama121032j0002 AMED Basis for Supporting Innovative Drug Discovery and Life Science Research: PHD/0096/2560 Thailand Science Research and Innovation Fundamental Fund: NRCT 820/2563 National Research Council of Thailand under the Research Team Promotion grant: 2I01 BX000972-05 Mike Slive Foundation for Prostate Cancer Research: P30CA086862
This work was supported by Japan Science and Technology Agency (JST) START University Ecosystem Promotion Type (Sup-porting Creation of Startup Ecosystem in Startup Cities), Grant Number JPMJST2281 to Y.T., by Grants-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology (MEXT), Grant Numbers 16K08844, 23K06677, and JP223fa627004 to Y.T., by Grants-in-Aid for Scientific Research from Japan Agency for Medical Research and Development (AMED), Grant Numbers A48 and A90 to Y.T., by Grant-in-Aid from AMED Basis for Supporting Innovative Drug Discovery and Life Science Research, Grant Number 23ama121032j0002 to Y.T., by Research Funding granted by Nagasaki University President Shigeru Kohno to Y.T., by Thailand Research Fund under the Royal Golden Jubilee Ph.D. Program, Grant number PHD/0096/2560 to I.K., by Thailand Science Research and Innovation Fundamental Fund and the National Research Council of Thailand under the Research Team Promotion grant, Grant Number NRCT 820/2563 to K.N.-B., by the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development 2I01 BX000972-05), the Mike Slive Foundation for Prostate Cancer Research, and the NIH National Cancer Institute Grants (P30CA086862 Oberley Award and Core Support) to C.T.M. C.T.M. is the Kelting Family Scholar in Rheumatology. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the granting agencies.
Language: English
Date published: 08/08/2024
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984696864202771

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