TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation against Cancer

Combination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in the treatment of many types of cancers and has become the mainstream in the comprehensive treatment of cancers. Ablation in combination with immunotherapy has achieved tremendous efficacy in some preclinical and clinical studies. To date, our team proved that ablation in combination with ICIs was a promising antitumor therapeutic strategy for the liver metastasis of colorectal cancer (CRC). Moreover, we found that the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was up-regulated after microwave ablation (MWA), indicating that TIGIT was involved in immunosuppression, and the combination of MWA and TIGIT blockade represented a potential clinical treatment strategy. In this study, we analyzed the single-cell RNA sequencing (scRNA-seq) data from the MWA and MWA plus anti-TIGIT groups. We found that TIGIT blockade in combination with MWA significantly promoted the expansion and functions of CD8+ TILs and reshaped myeloid cells in the tumor microenvironment (TME). In conclusion, TIGIT blockade in combination with MWA was a novel treatment strategy for the liver metastasis of CRC, and this combination therapy could reprogram the TME toward an antitumor environment. Overall design: MC38 tumor cells were subcutaneously inoculated into the bilateral flanks of C57BL/6 mice. MWA was only carried out on the tumor on the right flank when the tumor volume reached approximately 300 mm3. TIGIT blockade was administered intraperitoneally three times every 3 days starting 1 day after MWA. On day 8 after MWA treatment, tumor on the left side were isolated, digested and isolated CD45+ cells. Libraries were constructed using 10x Genomics.