| First Author | Edwards SC | Year | 2023 |
| Journal | J Exp Med | Volume | 220 |
| Issue | 2 | PubMed ID | 36480166 |
| Mgi Jnum | J:331888 | Mgi Id | MGI:7408043 |
| Doi | 10.1084/jem.20211431 | Citation | Edwards SC, et al. (2023) PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A-producing gammadelta T cells. J Exp Med 220(2) |
| abstractText | IL-17A-producing gammadelta T cells in mice consist primarily of Vgamma6+ tissue-resident cells and Vgamma4+ circulating cells. How these gammadelta T cell subsets are regulated during homeostasis and cancer remains poorly understood. Using single-cell RNA sequencing and flow cytommetry, we show that lung Vgamma4+ and Vgamma6+ cells from tumor-free and tumor-bearing mice express contrasting cell surface molecules as well as distinct co-inhibitory molecules, which function to suppress their expansion. Vgamma6+ cells express constitutively high levels of PD-1, whereas Vgamma4+ cells upregulate TIM-3 in response to tumor-derived IL-1beta and IL-23. Inhibition of either PD-1 or TIM-3 in mammary tumor-bearing mice increased Vgamma6+ and Vgamma4+ cell numbers, respectively. We found that genetic deletion of gammadelta T cells elicits responsiveness to anti-PD-1 and anti-TIM-3 immunotherapy in a mammary tumor model that is refractory to T cell checkpoint inhibitors, indicating that IL-17A-producing gammadelta T cells instigate resistance to immunotherapy. Together, these data demonstrate how lung IL-17A-producing gammadelta T cell subsets are differentially controlled by PD-1 and TIM-3 in steady-state and cancer. |
