Investigation of the efficacy and safety of cryoablation and intra-arterial PD-1 inhibitor in patients with advanced disease not responding to checkpoint inhibitors: An exploratory study.

Objective: To explore the effectiveness of cryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors in overcoming immune resistance in advanced solid cancers. Methods: In this pilot retrospective study, nine patients with solid cancers were treated with tumour cryoablation and arterial perfusion with programmed cell death protein 1 inhibitors, which had previously proven ineffective. The CIBERSORT software was used to estimate the levels of tumour-infiltrating immune cells in the challenged tumour. Changes in the levels of circulating T cells were assessed using flow cytometry. The primary endpoints were disease control and objective response rates, and the secondary endpoint was safety. Results: The nine patients with advanced solid tumours received cryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors between June and December 2021. The median follow-up time was 5.8 months. We recorded an objective response rate in two patients (22.22%). The best overall responses were partial responses in two patients (22.22%) and one case (11.11%) of stable disease, while six patients (66.67%) presented progressive disease. However, the median overall survival time was not reached. The median progression-free survival was 2.4 months. Treatment-related severe adverse events included one case of abdominal infection and one case of upper gastrointestinal bleeding, which were cured after the intervention. The CIBERSORT software confirmed the importance of cryoablation in regulating tumour-infiltrating immune cells. Thus, macrophage polarisation from the M2 to the M1 phenotype in the challenged tumour and a gradual increase in the levels of circulating CD4+ T cells were observed after administration of the combination therapy. Conclusion: Cryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors has the potential efficacy and safety to overcome immune resistance in patients with advanced solid cancers. The combination therapy leads to macrophage polarisation from the M2 to the M1 phenotype in the challenged tumour to enhance antitumour immunity.