Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells. / Powell, Richard M.; Peeters, Marlies J.W.; Rahbech, Anne; Aehnlich, Pia; Seremet, Tina; Straten, Per Thor.

In: Vaccines, Vol. 9, No. 11, 1294, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Powell, RM, Peeters, MJW, Rahbech, A, Aehnlich, P, Seremet, T & Straten, PT 2021, 'Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells', Vaccines, vol. 9, no. 11, 1294. https://doi.org/10.3390/vaccines9111294

APA

Powell, R. M., Peeters, M. J. W., Rahbech, A., Aehnlich, P., Seremet, T., & Straten, P. T. (2021). Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells. Vaccines, 9(11), [1294]. https://doi.org/10.3390/vaccines9111294

Vancouver

Powell RM, Peeters MJW, Rahbech A, Aehnlich P, Seremet T, Straten PT. Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells. Vaccines. 2021;9(11). 1294. https://doi.org/10.3390/vaccines9111294

Author

Powell, Richard M. ; Peeters, Marlies J.W. ; Rahbech, Anne ; Aehnlich, Pia ; Seremet, Tina ; Straten, Per Thor. / Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells. In: Vaccines. 2021 ; Vol. 9, No. 11.

Bibtex

@article{5718c96427c3466aa54c7c4196b4c3dd,
title = "Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells",
abstract = "There is an increasing interest in the development of Receptor Tyrosine Kinases inhibitors (RTKIs) for cancer treatment, as dysregulation of RTK expression can govern oncogenesis. Among the newer generations of RTKIs, many target Mer Tyrosine Kinase (MERTK) and Fms related RTK 3 (FLT3). Next to being overexpressed in many cancers, MERTK and FLT3 have important roles in immune cell development and function. In this study, we address how the new generation and potent RTKIs of MERTK/FLT3 affect human primary CD8+ T cell function. Using ex vivo T cell receptor (TCR)-activated CD8+ T cells, we demonstrate that use of dual MERTK/FLT3 inhibitor UNC2025 restricts CD8+ T proliferation at the G2 phase, at least in part by modulation of mTOR signaling. Cytokine production and activation remain largely unaffected. Finally, we show that activated CD8+ T cells express FLT3 from day two post activation, and FLT3 inhibition with AC220 (quizartinib) or siRNA-mediated knockdown affects cell cycle kinetics. These results signify that caution is needed when using potent RTKIs in the context of antitumor immune responses.",
keywords = "CD8 T cells, FLT3, MERTK, Receptor tyrosine kinases, Small molecule inhibitors, T lymphocytes",
author = "Powell, {Richard M.} and Peeters, {Marlies J.W.} and Anne Rahbech and Pia Aehnlich and Tina Seremet and Straten, {Per Thor}",
note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
doi = "10.3390/vaccines9111294",
language = "English",
volume = "9",
journal = "Vaccines",
issn = "2076-393X",
publisher = "MDPI AG",
number = "11",

}

RIS

TY - JOUR

T1 - Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells

AU - Powell, Richard M.

AU - Peeters, Marlies J.W.

AU - Rahbech, Anne

AU - Aehnlich, Pia

AU - Seremet, Tina

AU - Straten, Per Thor

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - There is an increasing interest in the development of Receptor Tyrosine Kinases inhibitors (RTKIs) for cancer treatment, as dysregulation of RTK expression can govern oncogenesis. Among the newer generations of RTKIs, many target Mer Tyrosine Kinase (MERTK) and Fms related RTK 3 (FLT3). Next to being overexpressed in many cancers, MERTK and FLT3 have important roles in immune cell development and function. In this study, we address how the new generation and potent RTKIs of MERTK/FLT3 affect human primary CD8+ T cell function. Using ex vivo T cell receptor (TCR)-activated CD8+ T cells, we demonstrate that use of dual MERTK/FLT3 inhibitor UNC2025 restricts CD8+ T proliferation at the G2 phase, at least in part by modulation of mTOR signaling. Cytokine production and activation remain largely unaffected. Finally, we show that activated CD8+ T cells express FLT3 from day two post activation, and FLT3 inhibition with AC220 (quizartinib) or siRNA-mediated knockdown affects cell cycle kinetics. These results signify that caution is needed when using potent RTKIs in the context of antitumor immune responses.

AB - There is an increasing interest in the development of Receptor Tyrosine Kinases inhibitors (RTKIs) for cancer treatment, as dysregulation of RTK expression can govern oncogenesis. Among the newer generations of RTKIs, many target Mer Tyrosine Kinase (MERTK) and Fms related RTK 3 (FLT3). Next to being overexpressed in many cancers, MERTK and FLT3 have important roles in immune cell development and function. In this study, we address how the new generation and potent RTKIs of MERTK/FLT3 affect human primary CD8+ T cell function. Using ex vivo T cell receptor (TCR)-activated CD8+ T cells, we demonstrate that use of dual MERTK/FLT3 inhibitor UNC2025 restricts CD8+ T proliferation at the G2 phase, at least in part by modulation of mTOR signaling. Cytokine production and activation remain largely unaffected. Finally, we show that activated CD8+ T cells express FLT3 from day two post activation, and FLT3 inhibition with AC220 (quizartinib) or siRNA-mediated knockdown affects cell cycle kinetics. These results signify that caution is needed when using potent RTKIs in the context of antitumor immune responses.

KW - CD8 T cells

KW - FLT3

KW - MERTK

KW - Receptor tyrosine kinases

KW - Small molecule inhibitors

KW - T lymphocytes

U2 - 10.3390/vaccines9111294

DO - 10.3390/vaccines9111294

M3 - Journal article

C2 - 34835225

AN - SCOPUS:85119584871

VL - 9

JO - Vaccines

JF - Vaccines

SN - 2076-393X

IS - 11

M1 - 1294

ER -

ID: 285798451