| First Author | Lozano T | Year | 2022 |
| Journal | Cancer Lett | Volume | 528 |
| Pages | 45-58 | PubMed ID | 34973390 |
| Mgi Jnum | J:318813 | Mgi Id | MGI:6860601 |
| Doi | 10.1016/j.canlet.2021.12.030 | Citation | Lozano T, et al. (2022) TCR-induced FOXP3 expression by CD8(+) T cells impairs their anti-tumor activity. Cancer Lett 528:45-58 |
| abstractText | Adoptive cell transfer therapy using CD8(+) T lymphocytes showed promising results eradicating metastatic malignancies. However, several regulatory mechanisms limit its efficacy. We studied the role of the expression of the transcription factor FOXP3 on CD8(+) T cell function and anti-tumor immunity. Here we show that suboptimal T cell receptor stimulation of CD8(+) T cells upregulates FOXP3 in vitro. Similarly, CD8 T cells transferred into tumor-bearing mice upregulate FOXP3 in vivo. Cell-intrinsic loss of FOXP3 by CD8(+) T cells resulted in improved functionality after TCR stimulation and better antitumor responses in vivo. Inhibition of the FOXP3/NFAT interaction likewise improved CD8(+) T cell functionality. Transcriptomic analysis of cells after TCR stimulation revealed an enrichment of genes implicated in the response to IFN-gamma, IFN-alpha, inflammatory response, IL-6/JAK/STAT, G2M checkpoint and IL-2/STAT signaling in FOXP3-deficient CD8(+) T cells with respect to FOXP3-wt CD8(+) T cells. Our results suggest that transient expression of FOXP3 by CD8(+) T cells in the tumor microenvironment restrains their anti-tumor activity, with clear implications for improving T cell responses during immunotherapy. |
