TGF-beta and IL-12 conversely orchestrate formation of CD103+ CD8 tumor-resident memory T cells to regulate response to therapeutic cancer vaccine [RNA-Seq]

Using mouse model, we show that CD8 tumor-infiltrating T lymphocytes (TIL) include two major resident T cells subpopulations expressing either CD49a or CD103 integrin, with a subset co-expressing CD103 and Tcf-1 transcription factor. Tumor vaccination induces a decrease in the percentage of Tcf-1+CD103+ TRM-like cells and an expansion of CD49a+ TRM displaying an effector/exhausted profile. Tcf-1+CD103+ TRM-cell density increases in tumors from vaccinated transgenic mice constitutively expressing active TGF-beta-type-2-receptor and wild-type mice challenged with neutralizing anti-IL-12 antibodies. Stimulation of mouse and human CD8 T cells with recombinant (r)TGF-beta combined with anti-CD3 antibodies results in increase in the proportion of CD103+ and Tcf-1+CD103+ CD8 T cells, whereas rIL-12 induces decrease in CD103 expression on CD8 T cells. Overall design: RNAseq was performed using Illumina Hiseq 200 on sorted CD103+, CD49a+ and CD103negCD49aneg CD8 TIL populations of 4 pools from 3x B16 melanoma tumors