Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer.
James ClarkeBharat PanwarAriel MadrigalDivya SinghRavindra GujarOliver WoodSerena J CheeSimon EschweilerEmma V KingAmiera S AwadChristopher J HanleyKaty J McCannSourya BhattacharyyaEdwin WooAiman AlzetaniGrégory SeumoisGareth J ThomasAnusha-Preethi GanesanPeter S FriedmannTilman Sanchez-ElsnerFerhat AyChristian Hermann OttensmeierPandurangan VijayanandPublished in: The Journal of experimental medicine (2019)
High numbers of tissue-resident memory T (TRM) cells are associated with better clinical outcomes in cancer patients. However, the molecular characteristics that drive their efficient immune response to tumors are poorly understood. Here, single-cell and bulk transcriptomic analysis of TRM and non-TRM cells present in tumor and normal lung tissue from patients with lung cancer revealed that PD-1-expressing TRM cells in tumors were clonally expanded and enriched for transcripts linked to cell proliferation and cytotoxicity when compared with PD-1-expressing non-TRM cells. This feature was more prominent in the TRM cell subset coexpressing PD-1 and TIM-3, and it was validated by functional assays ex vivo and also reflected in their chromatin accessibility profile. This PD-1+TIM-3+ TRM cell subset was enriched in responders to PD-1 inhibitors and in tumors with a greater magnitude of CTL responses. These data highlight that not all CTLs expressing PD-1 are dysfunctional; on the contrary, TRM cells with PD-1 expression were enriched for features suggestive of superior functionality.
Keyphrases
- single cell
- induced apoptosis
- cell cycle arrest
- cell proliferation
- gene expression
- high throughput
- poor prognosis
- endoplasmic reticulum stress
- oxidative stress
- patient safety
- dna methylation
- transcription factor
- dna damage
- stem cells
- signaling pathway
- mesenchymal stem cells
- working memory
- binding protein
- quality improvement
- data analysis