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

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
51 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number3770
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume21
Issue number11
DOIs
Publication statusPublished - Jun-2020

Keywords

  • 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

Cite this