{Reference Type}: Journal Article
{Title}: Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence.
{Author}: Dai D;Pei Y;Zhu B;Wang D;Pei S;Huang H;Zhu Q;Deng X;Ye J;Xu J;Chen X;Huang M;Xiao Y;
{Journal}: Cell Rep Med
{Volume}: 5
{Issue}: 5
{Year}: 2024 May 21
{Factor}: 16.988
{DOI}: 10.1016/j.xcrm.2024.101550
{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, 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.