Conclusions
These findings are paradigm-shifting given that chemotherapy is traditionally considered immunosuppressive. Our study reveals the novel effect of low-dose eribulin chemotherapy in inhibiting bladder tumor growth by enhancing anti-tumor NK cell immunity, challenging previous assumptions and opening new therapeutic approaches to improve antitumor immunity.
Methods
Here, we explore the effects of low-dose eribulin on direct NK cell activation in vitro, including on primary patient samples, and in vivo utilizing multiple murine models. Flow cytometry and RNA sequencing were employed to identify the mechanism of NK cell activation by eribulin, which was associated with increased migration and cytotoxicity of NK cells against BCa cells.
Results
We found that localized eribulin instillation significantly reduces bladder tumor burden and improves survival in primary BCa in an NK cell-dependent manner. Importantly, eribulin promoted the shift of patient-derived intratumoral NK cells towards an anti-tumor CD49a+ CD103+ NK subset (ieILC1-like) while diminishing the dysfunctional NR4A2-expressing CD49a- NK subset. Moreover, it decreased the overall expression of exhaustion markers on NK cells, a pattern replicated in our murine models. Conclusions: These findings are paradigm-shifting given that chemotherapy is traditionally considered immunosuppressive. Our study reveals the novel effect of low-dose eribulin chemotherapy in inhibiting bladder tumor growth by enhancing anti-tumor NK cell immunity, challenging previous assumptions and opening new therapeutic approaches to improve antitumor immunity.