Transcriptional Activity and Stability of CD39+CD103+CD8+T Cells in Human High-Grade Endometrial CancerWorkel, H. H., van Rooij, N., Plat, A., Spierings, D. C. J., Fehrmann, R. S. N., Nijman, H. W. & de Bruyn, M., Jun-2020, In : International Journal of Molecular Sciences. 21, 11, 18 p., 3770.
Research output: Contribution to journal › Article › Academic › peer-review
Tumor-infiltrating CD8+ T cells (TIL) are of the utmost importance in anti-tumor immunity. CD103 defines tumor-resident memory T cells (T-RM cells) associated with improved survival and response to immune checkpoint blockade (ICB) across human tumors. Co-expression of CD39 and CD103 marks tumor-specific T-RM with enhanced cytolytic potential, suggesting that CD39+CD103+ T-RM could be a suitable biomarker for immunotherapy. However, little is known about the transcriptional activity of T-RM cells in situ. We analyzed CD39+CD103+ T-RM 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+ T-RM cells were transcriptionally active and expressed a characteristic T-RM signature. Activated CD39+CD103+ T-RM 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+ T-RM cells are transcriptionally active T-RM cells with a polyfunctional, reactivation-responsive repertoire. Secondly, we hypothesize that differential regulation of transcript stability potentiates rapid responses upon T-RM reactivation in tumors.
|Number of pages||18|
|Journal||International Journal of Molecular Sciences|
|Publication status||Published - Jun-2020|
- tissue-resident memory cell, endometrial cancer, CD103, CD39, transcript stability, cytokinesis, IL-21, TUMOR-INFILTRATING LYMPHOCYTES, T-CELLS, NEOADJUVANT CHEMOTHERAPY, ACTINOMYCIN-D, MEMORY, INHIBITION, MICROENVIRONMENT, DIFFERENTIATION, ENGAGEMENT