Cryo-thermal therapy reprograms myeloid cells into CCL5+ mature phenotype to increase T cell infiltration and potentiates anti-PD-1 therapy

Cryo-thermal therapy (CTT) not only completely ablates local solid tumours by pre-freezing before radiofrequency heating, but also reverses immunosuppression and triggers strong systemic anti-tumour immunity to inhibit tumour recurrence and metastasis.

Our present study reveals that combining CTT with anti-PD-1 treatment potently enhances myeloid cell maturation and simultaneously promotes the infiltration and functional activation of T cells in distal tumours, resulting in superior suppression of distal tumour growth compared to either cryoablation or radiofrequency ablation combined with anti-PD-1. Mechanistically, CTT specifically induces TNF-α production in mature myeloid cells, triggering autocrine CCL5 secretion that recruits peripheral IFN-γ+ T cells induced by CTT in distal tumours, creating a cytokine loop where IFN-γ derived from T cells and TNF-α derived from myeloid cells collectively promote CCL5 secretion in myeloid cells to enhance effector T cell recruitment in distal tumours.