| Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence |
| Author |
Dai, DF; Pei, YF; Zhu, BQ; Wang, DQ; Pei, SY; Huang, H; Zhu, QC; Deng, XY; Ye, JL; Xu, J; Chen, XX; Huang, MZ; Xiao, YC |
| Journal |
CELL REPORTS MEDICINE |
| Pub Year |
2024 |
| Type |
|
| Abstract |
Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single -cell RNA sequencing reveal that CCRT specifically promotes CD8 + T cell senescence, driven by atypical chemokine receptor 2 (ACKR2) + CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2 + tumor cells are induced to produce transforming growth factor b to drive CD8 + T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8 + T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2 + tumor cells driving CD8 + T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8 + T cell senescence for chemoradiotherapy recurrence. |
| Issue |
5 |
| Volume |
5 |
| SCI |
11.7 |
