{
  "abstract": "Common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) is a multifunctional scavenger receptor expressed on tumor-associated macrophages (TAMs). In a recent study published in the Journal for ImmunoTherapy of Cancer, Yu et al reported that CLEVER-1+ TAMs accumulate in advanced gastric cancer (GC), associate with poor prognosis, and contribute to resistance to chemoimmunotherapy. CLEVER-1 blockade using bexmarilimab reprogrammed TAMs toward a pro-inflammatory phenotype by suppressing peroxisome proliferator-activated receptor gamma (PPARγ)-driven lipid metabolism and enhancing antigen presentation and inflammatory cytokine secretion. CLEVER-1 blockade also synergized with anti-programmed cell death protein 1 (PD-1) therapy in ex vivo GC models, particularly in tumors enriched with CLEVER-1+ TAM. These findings identify CLEVER-1+ TAMs as both biomarker and functional mediator of anti-PD-1 therapy resistance, providing a rationale for combining bexmarilimab with immune checkpoint blockade in GC. In this commentary, we discuss the mechanistic significance, translational potential, and clinical prospects of CLEVER-1 blockade to overcome immunotherapy resistance in GC.",
  "authors": [
    {
      "affiliations": [
        "Department of Colorectal Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China",
        "Provincial Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"
      ],
      "name": "Xiaonan Xiang"
    },
    {
      "affiliations": [
        "Department of Colorectal Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"
      ],
      "name": "Fei Wang"
    },
    {
      "affiliations": [
        "Department of Colorectal Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"
      ],
      "name": "Yanbin Shen"
    },
    {
      "affiliations": [
        "Department of Colorectal Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China",
        "Provincial Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"
      ],
      "name": "Sheng Dai"
    }
  ],
  "title": "CLEVER-1 blockade reprograms TAMs to overcome anti-PD-1 resistance in gastric cancer",
  "uid": "eef22b33-a355-53cd-80bb-551be906f0ed"
}