Weigelin B, Friedl P. T cell-mediated additive cytotoxicity – death by multiple bullets. Trends Cancer. 2022;8:980–7.
Article CAS PubMed Google Scholar
Nair S & Dhodapkar MV. Natural killer T cells in cancer immunotherapy. Front Immunol. 2017; 8. https://doi.org/10.3389/fimmu.2017.01178.
de Miguel D, et al. Inflammatory cell death induced by cytotoxic lymphocytes: a dangerous but necessary liaison. FEBS J. 2022;289:4398–415.
Martínez-Lostao L, Anel A, Pardo J. How do cytotoxic lymphocytes kill cancer cells? Clinical Cancer Res. 2015;21:5047–56.
Venkatesh H, Tracy SI & Farrar MA. Cytotoxic CD4 T cells in the mucosa and in cancer. Front Immunol. 2023; 14. https://doi.org/10.3389/fimmu.2023.1233261.
Jonsson AH, et al. Granzyme K+ CD8 T cells form a core population in inflamed human tissue. Sci Transl Med. 2022;14(649):eabo0686.
Capitani N, Patrussi L & Baldari CT. Nature vs. Nurture: The two opposing behaviors of cytotoxic t lymphocytes in the tumor microenvironment. Int J Mol Sci. 2021; 22. https://doi.org/10.3390/ijms222011221.
Torres RM, Turner JA, D’Antonio M, Pelanda R, Kremer KN. Regulation of CD8 T-cell signaling, metabolism, and cytotoxic activity by extracellular lysophosphatidic acid. Immunol Rev. 2023;317:203–22.
Article CAS PubMed Google Scholar
Lisci M, Griffiths GM. Arming a killer: mitochondrial regulation of CD8+ T cell cytotoxicity. Trends Cell Biol. 2023;33:138–47.
Article CAS PubMed Google Scholar
Harty JT, Badovinac VP. Shaping and reshaping CD8+ T-cell memory. Nat Rev Immunol. 2008;8:107–19.
Article CAS PubMed Google Scholar
Konduri V. et al. CD8+CD161+ T-Cells: Cytotoxic Memory Cells With High Therapeutic Potential. Front Immunol. 2021; 11. https://doi.org/10.3389/fimmu.2020.613204.
Al Moussawy M & Abdelsamed HA. Non-cytotoxic functions of CD8 T cells: “repentance of a serial killer”. Front Immunol. 2022; 13. https://doi.org/10.3389/fimmu.2022.1001129.
Wagner H, Götze D, Ptschelinzew L, Röllinghoff M. Induction of cytotoxic T lymphocytes against I-region-coded determinants: in vitro evidence for a third histocompatibility locus in the mouse. J Exp Med. 1975;142:1477–87.
Article CAS PubMed Google Scholar
Takeuchi A & Saito T. CD4 CTL, a cytotoxic subset of CD4+ T cells, their differentiation and function. Front Immunol. 2017; 8. https://doi.org/10.3389/fimmu.2017.00194.
Xie Y, et al. Naive tumor-specific CD4+ T cells differentiated in vivo eradicate established melanoma. J ExpMed. 2010;207:651–67.
Quezada SA, et al. Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med. 2010;207:637–50.
Article CAS PubMed PubMed Central Google Scholar
van de Berg PJ, van Leeuwen EM, ten Berge IJ, van Lier R. Cytotoxic human CD4+ T cells. Curr Opin Immunol. 2008;20:339–43.
Juno JA. et al. Cytotoxic CD4 T cells-friend or foe during viral infection? Front Immunol. 2017; 8. https://doi.org/10.3389/fimmu.2017.00019.
Freuchet A, et al. Identification of human exTreg cells as CD16+CD56+ cytotoxic CD4+ T cells. Nat Immunol. 2023;24:1748–61.
Article CAS PubMed Google Scholar
Fisch P, et al. Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis. J Exp Med. 1990;171:1567–79.
Article CAS PubMed Google Scholar
Silva-Santos B, Serre K, Norell H. γδ T cells in cancer. Nat Rev Immunol. 2015;15:683–91.
Article CAS PubMed Google Scholar
Chitadze G, Oberg H-H, Wesch D, Kabelitz D. The Ambiguous role of γδ T lymphocytes in antitumor immunity. Trends Immunol. 2017;38:668–78.
Article CAS PubMed Google Scholar
Doherty DG, Dunne MR, Mangan BA, Madrigal-Estebas L. Preferential Th1 cytokine profile of phosphoantigen-stimulated human v 9V 2 T cells. Mediators Inflamm. 2010;2010:704941.
Mao Y, et al. A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells. Cell Mol Immunol. 2016;13:217–28.
Article CAS PubMed Google Scholar
Caccamo N, et al. Differentiation, phenotype, and function of interleukin-17–producing human Vγ9Vδ2 T cells. Blood. 2011;118:129–38.
Article CAS PubMed Google Scholar
Harmon C, et al. γδ T cell dichotomy with opposing cytotoxic and wound healing functions in human solid tumors. Nat Cancer. 2023;4:1122–37.
Article CAS PubMed Google Scholar
Raverdeau M, Cunningham SP, Harmon C, Lynch L. γδ T cells in cancer: a small population of lymphocytes with big implications. Clin Transl Immunol. 2019;8:e01080.
Holderness J, Hedges JF, Ramstead A, Jutila MA. Comparative biology of γδ T cell function in humans, mice, and domestic animals. Annu Rev Anim Biosci. 2013;1:99–124.
Niu C, et al. In vitro analysis of the proliferative capacity and cytotoxic effects of ex vivo induced natural killer cells, cytokine-induced killer cells, and gamma-delta T cells. BMC Immunol. 2015;16:61.
Pizzolato G, et al. Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes. Proc Natl Acad Sci U S A. 2019;116:11906–15.
Article ADS CAS PubMed PubMed Central Google Scholar
Almeida AR, et al. Delta one T cells for immunotherapy of chronic lymphocytic leukemia: clinical-grade expansion/differentiation and preclinical proof of concept. Clin Cancer Res. 2016;22:5795–804.
Article CAS PubMed Google Scholar
Halim L, Parente-Pereira AC, Maher J. Prospects for immunotherapy of acute myeloid leukemia using γδ T cells. Immunotherapy. 2017;9:111–4.
Article CAS PubMed Google Scholar
Fisher JPH, et al. Neuroblastoma killing properties of Vδ2 and Vδ2-negative γδT cells following expansion by artificial antigen-presenting cells. Clin Cancer Res. 2014;20:5720–32.
Article ADS CAS PubMed PubMed Central Google Scholar
Chan KF, Duarte JDG, Ostrouska S & Behren A. γδ T Cells in the Tumor Microenvironment—Interactions With Other Immune Cells. Front Immunol. 2022; 13. https://doi.org/10.3389/fimmu.2022.894315.
Pont F, et al. The gene expression profile of phosphoantigen-specific human γδ T lymphocytes is a blend of αβ T-cell and NK-cell signatures. Eur J Immunol. 2012;42:228–40.
Article CAS PubMed Google Scholar
Kratzmeier C, Singh S, Asiedu EB, Webb TJ. Current Developments in the Preclinical and Clinical use of Natural Killer T cells. Bio Drugs. 2023;37:57–71. https://doi.org/10.1007/s40259-022-00572-4.
Nakashima, H. & Kinoshita, M. Antitumor Immunity Exerted by Natural Killer and Natural Killer T Cells in the Liver. J Clin Med. 2023; 12. https://doi.org/10.3390/jcm12030866.
Crosby CM, Kronenberg M. Tissue-specific functions of invariant natural killer T cells. Nat Rev Immunol. 2018;18:559–74. https://doi.org/10.1038/s41577-018-0034-2.
Article CAS PubMed PubMed Central Google Scholar
Bassiri H, et al. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo. Cancer Immunol Res. 2014;2:59–69.
Article CAS PubMed Google Scholar
Perna SK, et al. Interleukin-7 Mediates Selective Expansion of Tumor-redirected Cytotoxic T Lymphocytes (CTLs) without Enhancement of Regulatory T-cell Inhibition. Clin Cancer Res. 2014;20:131–9.
Article CAS PubMed Google Scholar
Ihara F, et al. Regulatory T cells induce CD4− NKT cell anergy and suppress NKT cell cytotoxic function. Cancer Immunol Immunother. 2019;68:1935–47.
Article CAS PubMed Google Scholar
Konishi J, et al. The characteristics of human NKT cells in lung cancer—CD1d independent cytotoxicity against lung cancer cells by NKT cells and decreased human NKT cell response in lung cancer patients. Hum Immunol. 2004;65:1377–88.
Article CAS PubMed Google Scholar
Díaz-Basabe A, et al. Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway. Mol Oncol. 2021;15:3385–403.
Article PubMed PubMed Central Google Scholar
Cachot A, et al. Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer. Sci Adv. 2021;7(9):eabe3348.
Hoeks C, Duran G, Hellings N & Broux B. When Helpers Go Above and Beyond: Development and Characterization of Cytotoxic CD4+ T Cells. Front Immunol. 2022; 13. https://doi.org/10.3389/fimmu.2022.951900.
Peters PJ, et al. Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med. 1991;173(5):1099-109.
Ng SS, et al. The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation. Nat Immunol. 2020;21:1205–18.
Article PubMed PubMed Central Google Scholar
Cenerenti, M., Saillard, M., Romero, P. & Jandus, C. The Era of Cytotoxic CD4 T Cells. Front Immunol. 2022; 13. https://doi.org/10.3389/fimmu.2022.867189.
Fasth AER, Björkström NK, Anthoni M, Malmberg K-J, Malmström V. Activating NK-cell receptors co-stimulate CD4+CD28− T cells in patients with rheumatoid arthritis. Eur J Immunol. 2010;40:378–87.
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