| First Author | Zappasodi R | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 6 | Pages | 1017-1032.e7 |
| PubMed ID | 29894689 | Mgi Jnum | J:262546 |
| Mgi Id | MGI:6162394 | Doi | 10.1016/j.ccell.2018.05.009 |
| Citation | Zappasodi R, et al. (2018) Non-conventional Inhibitory CD4(+)Foxp3(-)PD-1(hi) T Cells as a Biomarker of Immune Checkpoint Blockade Activity. Cancer Cell 33(6):1017-1032.e7 |
| abstractText | A significant proportion of cancer patients do not respond to immune checkpoint blockade. To better understand the molecular mechanisms underlying these treatments, we explored the role of CD4(+)Foxp3(-) T cells expressing PD-1 (4PD1(hi)) and observed that 4PD1(hi) accumulate intratumorally as a function of tumor burden. Interestingly, CTLA-4 blockade promotes intratumoral and peripheral 4PD1(hi) increases in a dose-dependent manner, while combination with PD-1 blockade mitigates this effect and improves anti-tumor activity. We found that lack of effective 4PD1(hi) reduction after anti-PD-1 correlates with poor prognosis. Mechanistically, we provide evidence that mouse and human circulating and intra-tumor 4PD1(hi) inhibit T cell functions in a PD-1/PD-L1 dependent fashion and resemble follicular helper T cell (TFH)-like cells. Accordingly, anti-CTLA-4 activity is improved in TFH deficient mice. |
