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Tumor-infiltrating CD8+ T cells (TIL) are of the utmost importance in anti-tumor immunity. CD103 defines tumor-resident memory T cells (T 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 with enhanced cytolytic potential, suggesting that CD39+CD103+ T could be a suitable biomarker for immunotherapy. However, little is known about the transcriptional activity of T cells in situ. We analyzed CD39+CD103+ T cells sorted from human high-grade endometrial cancers ( = 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 cells were transcriptionally active and expressed a characteristic T signature. Activated CD39+CD103+ T cells differentially expressed , , and , and cytokine genes , , , (GM-CSF), and . 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 cells are transcriptionally active T cells with a polyfunctional, reactivation-responsive repertoire. Secondly, we hypothesize that differential regulation of transcript stability potentiates rapid responses upon T reactivation in tumors.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312498 | PMC |
| http://dx.doi.org/10.3390/ijms21113770 | DOI Listing |
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