Enhanced immune response of cryoablation combined with anti-CTLA-4 mAb against murine tumor draining lymph nodes of prostate cancer / 中国肿瘤临床

ABSTRACT

Objective: To evaluate the effect of immune response of cryoablation combined with anti-CTLA-4 mAb against murine tumor draining lymph nodes (TDLNs) of prostate cancer (PCa). Methods: PCa-bearing murine models were established and mice were divided randomly into 4 groups-control (A), cryoablation treatment (B), cryoablation combined with anti-CTLA-4 mAb treatment (C), and anti-CTLA-4 mAb treatment (D). TDLN specimens were obtained from 5 mice of each group at 4 time points before treatment, and 7, 14, and 21 days after treatment. Tumor size was measured at each time point. Flow cytometry was utilized to detect changes inTreg and CTL proportions in TDLNs. LDH was utilized to detect killing activity for tumor cells of CTL. Overall survival (OS) of each group was recorded. Results: Fourteen days after treatment, compared with that of group A, Treg proportion in group B (9.78%±1.88% vs. 6.02%±0.44%) and C (9.78%±1.88% vs. 6.03%±0.45%) was decreased (both P<0.05); compared with that of group A, CTL proportion of group B (27.34%±2.13% vs . 34.23%±1.15%), C (27.34%±2.13% vs. 52.21%±2.53%), and D (27.34±2.13% vs. 33.99±1.21) was increased (P<0.05, P<0.001, P<0.05); compared with those of group A, CTL killing activities of group B (13.32%±3.39% vs . 26.36%±2.95%), C (13.32%±3.39% vs . 45.25%±3.27%), and D (13.32%±3.39% vs. 25.31%±3.24%) were improved (P<0.05, P<0.001, P<0.05). Survival analysis showed that the OS of PCa-bearing mice were prolonged (P<0.05, P<0.001) in group B (25.60 d±1.52 d vs. 34.20d±6.98 d) and C (25.60 d±1.52 d vs. 43.60 d±2.88 d) compared with that of group A; OS was prolonged (P<0.05) in group C compared with that of group B (34.20d±6.98 d vs. 43.60d±2.88 d). Conclusions: Cryoablation combined with anti-CTLA-4 mAb can reduce the proportions of Tregs in the TDLNs, increase the proportions of CTL as well as killing activities, and significantly prolong OS of mice. However, the specific mechanism needs further study.