| First Author | Zhao B | Year | 2022 |
| Journal | Nat Immunol | Volume | 23 |
| Issue | 11 | Pages | 1588-1599 |
| PubMed ID | 36266363 | Mgi Jnum | J:333048 |
| Mgi Id | MGI:7408620 | Doi | 10.1038/s41590-022-01326-8 |
| Citation | Zhao B, et al. (2022) SUSD2 suppresses CD8(+) T cell antitumor immunity by targeting IL-2 receptor signaling. Nat Immunol 23(11):1588-1599 |
| abstractText | Dysfunctional CD8(+) T cells, which have defective production of antitumor effectors, represent a major mediator of immunosuppression in the tumor microenvironment. Here, we show that SUSD2 is a negative regulator of CD8(+) T cell antitumor function. Susd2(-/-) effector CD8(+) T cells showed enhanced production of antitumor molecules, which consequently blunted tumor growth in multiple syngeneic mouse tumor models. Through a quantitative mass spectrometry assay, we found that SUSD2 interacted with interleukin (IL)-2 receptor alpha through sushi domain-dependent protein interactions and that this interaction suppressed the binding of IL-2, an essential cytokine for the effector functions of CD8(+) T cells, to IL-2 receptor alpha. SUSD2 was not expressed on regulatory CD4(+) T cells and did not affect the inhibitory function of these cells. Adoptive transfer of Susd2(-/-) chimeric antigen receptor T cells induced a robust antitumor response in mice, highlighting the potential of SUSD2 as an immunotherapy target for cancer. |
