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

Abstract

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.

High-dimensional single-cell analysis delineates radiofrequency ablation induced immune microenvironmental remodeling in pancreatic cancer

“…To further assess the immune changes, we employed scRNA-seq and TCR profiles analysis approaches to profile immune cells infiltrating in distant non-RFA tumors after RFA treatment. In contrast to some previous studies 37 that showed that incomplete ablation of a target tumor was associated with new metastases and poor survival and reduced efficacy of anti-PD-1 immunotherapy, our study did not detect the myeloid-derived suppressor cells in the distant non-RFA tumor after RFA treatment. Furthermore, our study presents a comprehensive view of the cellular dynamics induced by RFA in distant tumors.…”

Ultrasound Molecular Imaging as a Potential Non-invasive Diagnosis to Detect the Margin of Hepatocarcinoma via CSF-1R Targeting

“…Researches have shown that RFA can lead to acute serologic elevation of active cytokines such as IL-6, nMDSC, and mMDSC, and a sustained high infiltration level of macrophages in the residual tumor (Shi et al, 2019;Sugimoto et al, 2019). In this study, CSF-1R was found highly expressed at the tumor boundary in patients with HCC, and also highly expressed in macrophages, but not tumor cells; making CSF-1R a feasible target.…”

Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma

“…Tumour biopsies revealed that PD-1 expression was increased on the T cell surfaces and a higher number of tumour infiltrating T cells was observed following the combination treatment, especially CD8+ T cells [ 40 ]. On the contrary, incomplete percutaneous ablation may worsen the prognosis and induce immunotherapy resistance, as reported in a mouse model of metastatic colorectal cancer [ 41 ].…”