| First Author | Do P | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 9 | Pages | 2806-2816 |
| PubMed ID | 30910862 | Mgi Jnum | J:274899 |
| Mgi Id | MGI:6296859 | Doi | 10.4049/jimmunol.1801359 |
| Citation | Do P, et al. (2019) Leukemic B Cell CTLA-4 Suppresses Costimulation of T Cells. J Immunol 202(9):2806-2816 |
| abstractText | The clinical benefit of CTLA-4 blockade on T cells is known, yet the impact of its expression on cancer cells remains unaddressed. We define an immunosuppressive role for tumor-expressed CTLA-4 using chronic lymphocytic leukemia (CLL) as a disease model. CLL cells, among other cancer cells, are CTLA-4(+) Coculture with activated human T cells induced surface CTLA-4 on primary human CLL B cells. CTLA-4 on CLL-derived human cell lines decreased CD80 expression on cocultured CD80(+) cells, with restoration upon CTLA-4 blockade. Coculture of CTLA-4(+) CLL cells with CD80-GFP(+) cell lines revealed transfer of CD80-GFP into CLL tumor cells, similar to CTLA-4(+) T cells able to trans-endocytose CD80. Coculture of T cells with CTLA-4(+) CLL cells decreased IL-2 production. Using a human CTLA-4 knock-in mouse lacking FcgammaR function, antitumor efficacy was observed by blocking murine CTLA-4 on tumor cells in isolation of the T cell effect and Fc-mediated depletion. These data implicate tumor CTLA-4 in cancer cell-mediated immunosuppression in vitro and as having a functional role in tumor cells in vivo. |
