As one of the peroxisome-proliferator-activated receptors (PPARs) family members (PPARα, PPARγ, and PPARδ), PPARδ regulates cell proliferation, metabolism, inflammation, autophagy and tumor progression (Gou et al., 2020b; Hou et al., 2012, 2013; Michalik et al., 2004; Zhang et al., 2013). PPARδ belongs to the nuclear hormone transcription factors, which could bind the targeted gene promoters with PPRE motif (AGGTCANAGGTCA) and regulates their gene expressions (Gou et al., 2017; You et al., 2015). Among of PPARs, PPARδ was first identified in humans (Schmidt et al., 1992). In colon cancer cells, activation of PPARδ by its agonists increases glucose and glutamine uptake, which is associated with promotion of Glut1 and SLC1A5 gene expressions (Zhang et al., 2017). Intestinal specific overexpression of PPARδ promotes colonic tumorigenesis in FVB mice in response to azoxymethane (Zuo et al., 2014). In contrast, loss of PPARδ inhibits COX-2 production and alleviates pro-inflammatory response (Wang et al., 2014), and COX-2 inhibitors (COXIBs, indomethacin) could inhibit PPARδ-induced tumorigenesis (You et al., 2015). GSK0660 is one of the PPARδ antagonists, which could reduce eNOS expression in endothelial cell (Tian et al., 2023). However, it is still unclear the effect of PPARδ antagonist on tumor immune evasion. PD-1/PD-L1 is a “don't find me” signal, which is an important immune checkpoint to regulate tumor immune escape (Topalian et al., 2012). Here we found that GSK0660 significantly inhibited colorectal tumor immune escape.