Chemoradiotherapy-induced ACKR2⁺ tumor cells drive CD8⁺ T cell senescence and cervical cancer recurrence.

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 β to drive CD8⁺ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospectiv

SUBMITTER: Dai D 

PROVIDER: S-EPMC11148771 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature