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Open AccessArticle

Transcriptional Activity and Stability of CD39+CD103+CD8+ T Cells in Human High-Grade Endometrial Cancer

1
Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
2
European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
3
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(11), 3770; https://doi.org/10.3390/ijms21113770
Received: 29 April 2020 / Revised: 21 May 2020 / Accepted: 22 May 2020 / Published: 27 May 2020
(This article belongs to the Special Issue Cancer Immunoediting and Beyond)
Tumor-infiltrating CD8+ T cells (TIL) are of the utmost importance in anti-tumor immunity. CD103 defines tumor-resident memory T cells (TRM cells) associated with improved survival and response to immune checkpoint blockade (ICB) across human tumors. Co-expression of CD39 and CD103 marks tumor-specific TRM with enhanced cytolytic potential, suggesting that CD39+CD103+ TRM could be a suitable biomarker for immunotherapy. However, little is known about the transcriptional activity of TRM cells in situ. We analyzed CD39+CD103+ TRM cells sorted from human high-grade endometrial cancers (n = 3) using mRNA sequencing. Cells remained untreated or were incubated with PMA/ionomycin (activation), actinomycin D (a platinum-like chemotherapeutic that inhibits transcription), or a combination of the two. Resting CD39+CD103+ TRM cells were transcriptionally active and expressed a characteristic TRM signature. Activated CD39+CD103+ TRM cells differentially expressed PLEK, TWNK, and FOS, and cytokine genes IFNG, TNF, IL2, CSF2 (GM-CSF), and IL21. Findings were confirmed using qPCR and cytokine production was validated by flow cytometry of cytotoxic TIL. We studied transcript stability and found that PMA-responsive genes and mitochondrial genes were particularly stable. In conclusion, CD39+CD103+ TRM cells are transcriptionally active TRM cells with a polyfunctional, reactivation-responsive repertoire. Secondly, we hypothesize that differential regulation of transcript stability potentiates rapid responses upon TRM reactivation in tumors. View Full-Text
Keywords: tissue-resident memory cell; endometrial cancer; CD103; CD39; transcript stability; cytokinesis; IL-21 tissue-resident memory cell; endometrial cancer; CD103; CD39; transcript stability; cytokinesis; IL-21
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MDPI and ACS Style

Workel, H.H.; van Rooij, N.; Plat, A.; Spierings, D.C.J.; Fehrmann, R.S.N.; Nijman, H.W.; de Bruyn, M. Transcriptional Activity and Stability of CD39+CD103+CD8+ T Cells in Human High-Grade Endometrial Cancer. Int. J. Mol. Sci. 2020, 21, 3770. https://doi.org/10.3390/ijms21113770

AMA Style

Workel HH, van Rooij N, Plat A, Spierings DCJ, Fehrmann RSN, Nijman HW, de Bruyn M. Transcriptional Activity and Stability of CD39+CD103+CD8+ T Cells in Human High-Grade Endometrial Cancer. International Journal of Molecular Sciences. 2020; 21(11):3770. https://doi.org/10.3390/ijms21113770

Chicago/Turabian Style

Workel, Hagma H.; van Rooij, Nienke; Plat, Annechien; Spierings, Diana C.J.; Fehrmann, Rudolf S.N.; Nijman, Hans W.; de Bruyn, Marco. 2020. "Transcriptional Activity and Stability of CD39+CD103+CD8+ T Cells in Human High-Grade Endometrial Cancer" Int. J. Mol. Sci. 21, no. 11: 3770. https://doi.org/10.3390/ijms21113770

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