CD39 Identifies the CD4+ Tumor-Specific T-cell Population in Human Cancer.
Kim E KortekaasSaskia J SantegoetsGregor SturmIlina EhsanSylvia L van EgmondFrancesca FinotelloZlatko TrajanoskiMarij J P WeltersMariette I E van PoelgeestSjoerd H Van der BurgPublished in: Cancer immunology research (2020)
The accumulation of tumor-specific CD4+ and CD8+ effector T cells is key to an effective antitumor response. Locally, CD4+ T cells promote the recruitment and effector function of tumor-specific CD8+ T cells and activate innate killer cells in the tumor. Here, we show that tumor-specific CD4+ T cells were predominantly present in the CD39+ subset of tumor-infiltrating lymphocytes (TIL). The CD39+ CD4+ and CD8+ TILs were detected in three different tumor types, and displayed an activated (PD-1+, HLA-DR+) effector memory phenotype. CD4+CD39+ single-cell RNA-sequenced TILs shared similar well-known activation, tissue residency, and effector cell-associated genes with CD8+CD39+CD103+ TILs. Finally, analysis of directly ex vivo cell-sorted and in vitro expanded pure populations of CD39-positive and negative CD4+ and CD8+ TILs revealed that tumor-specific antigen reactivity was almost exclusively detected among CD39+ cells. Immunotherapy of cancer is based on the activation of tumor-reactive CD4+ and CD8+ T cells. We show that the expression of CD39 can be used to identify, isolate, and expand tumor-reactive T-cell populations in cancers.
Keyphrases
- single cell
- immune response
- endothelial cells
- squamous cell carcinoma
- induced apoptosis
- dna methylation
- rna seq
- mesenchymal stem cells
- oxidative stress
- high throughput
- cell death
- genome wide
- papillary thyroid
- working memory
- cell proliferation
- cell cycle arrest
- lymph node metastasis
- emergency medicine
- type iii
- bioinformatics analysis