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Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner

Invariant natural killer T (iNKT) cells are innate‐like CD1d‐restricted T cells that express the invariant T cell receptor (TCR) composed of Vα24 and Vβ11 in humans. iNKT cells specifically recognize glycolipid antigens such as α‐galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct...

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Autores principales: Aoki, Takahiro, Takami, Mariko, Takatani, Tomozumi, Motoyoshi, Kiwamu, Ishii, Ayana, Hara, Ayaka, Toyoda, Takahide, Okada, Reona, Hino, Moeko, Koyama‐Nasu, Ryo, Kiuchi, Masahiro, Hirahara, Kiyoshi, Kimura, Motoko Y., Nakayama, Toshinori, Shimojo, Naoki, Motohashi, Shinichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385353/
https://www.ncbi.nlm.nih.gov/pubmed/32324315
http://dx.doi.org/10.1111/cas.14428
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author Aoki, Takahiro
Takami, Mariko
Takatani, Tomozumi
Motoyoshi, Kiwamu
Ishii, Ayana
Hara, Ayaka
Toyoda, Takahide
Okada, Reona
Hino, Moeko
Koyama‐Nasu, Ryo
Kiuchi, Masahiro
Hirahara, Kiyoshi
Kimura, Motoko Y.
Nakayama, Toshinori
Shimojo, Naoki
Motohashi, Shinichiro
author_facet Aoki, Takahiro
Takami, Mariko
Takatani, Tomozumi
Motoyoshi, Kiwamu
Ishii, Ayana
Hara, Ayaka
Toyoda, Takahide
Okada, Reona
Hino, Moeko
Koyama‐Nasu, Ryo
Kiuchi, Masahiro
Hirahara, Kiyoshi
Kimura, Motoko Y.
Nakayama, Toshinori
Shimojo, Naoki
Motohashi, Shinichiro
author_sort Aoki, Takahiro
collection PubMed
description Invariant natural killer T (iNKT) cells are innate‐like CD1d‐restricted T cells that express the invariant T cell receptor (TCR) composed of Vα24 and Vβ11 in humans. iNKT cells specifically recognize glycolipid antigens such as α‐galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct cytotoxicity toward CD1d‐positive tumor cells, especially when CD1d presents glycolipid antigens. However, iNKT cell recognition of CD1d‐negative tumor cells is unknown, and direct cytotoxicity of iNKT cells toward CD1d‐negative tumor cells remains controversial. Here, we demonstrate that activated iNKT cells recognize leukemia cells in a CD1d‐independent manner, however still in a TCR‐mediated way. iNKT cells degranulated and released Th1 cytokines toward CD1d‐negative leukemia cells (K562, HL‐60, REH) as well as αGalCer‐loaded CD1d‐positive Jurkat cells. The CD1d‐independent cytotoxicity was enhanced by natural killer cell‐activating receptors such as NKG2D, 2B4, DNAM‐1, LFA‐1 and CD2, but iNKT cells did not depend on these receptors for the recognition of CD1d‐negative leukemia cells. In contrast, TCR was essential for CD1d‐independent recognition and cytotoxicity. iNKT cells degranulated toward patient‐derived leukemia cells independently of CD1d expression. iNKT cells targeted myeloid malignancies more than acute lymphoblastic leukemia. These findings reveal a novel anti–tumor mechanism of iNKT cells in targeting CD1d‐negative tumor cells and indicate the potential of iNKT cells for clinical application to treat leukemia independently of CD1d.
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spelling pubmed-73853532020-07-30 Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner Aoki, Takahiro Takami, Mariko Takatani, Tomozumi Motoyoshi, Kiwamu Ishii, Ayana Hara, Ayaka Toyoda, Takahide Okada, Reona Hino, Moeko Koyama‐Nasu, Ryo Kiuchi, Masahiro Hirahara, Kiyoshi Kimura, Motoko Y. Nakayama, Toshinori Shimojo, Naoki Motohashi, Shinichiro Cancer Sci Original Articles Invariant natural killer T (iNKT) cells are innate‐like CD1d‐restricted T cells that express the invariant T cell receptor (TCR) composed of Vα24 and Vβ11 in humans. iNKT cells specifically recognize glycolipid antigens such as α‐galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct cytotoxicity toward CD1d‐positive tumor cells, especially when CD1d presents glycolipid antigens. However, iNKT cell recognition of CD1d‐negative tumor cells is unknown, and direct cytotoxicity of iNKT cells toward CD1d‐negative tumor cells remains controversial. Here, we demonstrate that activated iNKT cells recognize leukemia cells in a CD1d‐independent manner, however still in a TCR‐mediated way. iNKT cells degranulated and released Th1 cytokines toward CD1d‐negative leukemia cells (K562, HL‐60, REH) as well as αGalCer‐loaded CD1d‐positive Jurkat cells. The CD1d‐independent cytotoxicity was enhanced by natural killer cell‐activating receptors such as NKG2D, 2B4, DNAM‐1, LFA‐1 and CD2, but iNKT cells did not depend on these receptors for the recognition of CD1d‐negative leukemia cells. In contrast, TCR was essential for CD1d‐independent recognition and cytotoxicity. iNKT cells degranulated toward patient‐derived leukemia cells independently of CD1d expression. iNKT cells targeted myeloid malignancies more than acute lymphoblastic leukemia. These findings reveal a novel anti–tumor mechanism of iNKT cells in targeting CD1d‐negative tumor cells and indicate the potential of iNKT cells for clinical application to treat leukemia independently of CD1d. John Wiley and Sons Inc. 2020-06-19 2020-07 /pmc/articles/PMC7385353/ /pubmed/32324315 http://dx.doi.org/10.1111/cas.14428 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Aoki, Takahiro
Takami, Mariko
Takatani, Tomozumi
Motoyoshi, Kiwamu
Ishii, Ayana
Hara, Ayaka
Toyoda, Takahide
Okada, Reona
Hino, Moeko
Koyama‐Nasu, Ryo
Kiuchi, Masahiro
Hirahara, Kiyoshi
Kimura, Motoko Y.
Nakayama, Toshinori
Shimojo, Naoki
Motohashi, Shinichiro
Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner
title Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner
title_full Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner
title_fullStr Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner
title_full_unstemmed Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner
title_short Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner
title_sort activated invariant natural killer t cells directly recognize leukemia cells in a cd1d‐independent manner
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385353/
https://www.ncbi.nlm.nih.gov/pubmed/32324315
http://dx.doi.org/10.1111/cas.14428
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