Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy

作者：Liangrong Shi, Junjun Wang, Nianhua Ding, Yi Zhang, Yibei Zhu, Shunli Dong, Xiaohui Wang, Changli Peng, Chunhui Zhou, Ledu Zhou, Xiaodong Li, Hongbing Shi, Wei Wu, Xueyin Long, Changping Wu, Weihua Liao · 发表于：Nature Communications · 年份：2019 · DOI：10.1038/s41467-019-13204-3 · 被引用次数：285 · 研究领域：Cancer Immunotherapy and Biomarkers、Phagocytosis and Immune Regulation、Immune cells in cancer

Radiofrequency ablation (RFA) promotes tumor antigen-specific T cell responses and enhances the effect of immunotherapy in preclinical settings. Here we report that the existence of remnant tumor masses due to incomplete RFA (iRFA) is associated with earlier new metastases and poor survival in patients with colorectal cancer liver metastases (CRCLM). Using mouse models, we demonstrate that iRFA promotes tumor progression and hinders the efficacy of anti-PD-1 therapy. Immune analysis reveals that iRFA induces sustained local inflammation with predominant myeloid suppressor cells, which inhibit T cell function in tumors. Mechanistically, tumor cell-derived CCL2 is critical for the accumulation of monocytes and tumor-associated macrophages (TAMs). The crosstalk between TAMs and tumor cells enhances the CCL2 production by tumor cells. Furthermore, we find that administration of a CCR2 antagonist or the loss of CCL2 expression in tumor cells enhances the antitumor activity of PD-1 blockade, providing a salvage alternative for residual tumors after iRFA.