Other
19 Authors
- Su J,
- Wei J,
- Tartarone A,
- Yang Y,
- Carbonelli C,
- Dayyani F,
- Velotta JB,
- Zhang Y,
- Gabriel E,
- Liu Z,
- Kidane B,
- Wang Y,
- Wang F,
- Ma Y,
- Li Z,
- Ma N,
- Chen H,
- Long L,
- Wakefield CJ
| First Author | Liu Z | Year | 2023 |
| Journal | Cancer Cell | Volume | 41 |
| Issue | 11 | Pages | 1852-1870.e9 |
| PubMed ID | 37832554 | Mgi Jnum | J:357476 |
| Mgi Id | MGI:7550270 | Doi | 10.1016/j.ccell.2023.09.011 |
| Citation | Liu Z, et al. (2023) Progenitor-like exhausted SPRY1(+)CD8(+) T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma. Cancer Cell 41(11):1852-1870.e9 |
| abstractText | Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8(+) T cells expressing SPRY1 (CD8(+) Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8(+) Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8(+) T cells enforces Tpex phenotype and enhances ICB efficacy. Additionally, CD8(+) Tex-SPRY1 cells contribute to proinflammatory phenotype of macrophages and functional state of B cells, which thereby promotes antitumor immunity by enhancing CD8(+) T cell effector functions. Overall, our findings unravel progenitor-like CD8(+) Tex-SPRY1 cells' role in effective responses to ICB for ESCC and inform mechanistic biomarkers for future individualized immunotherapy. |
