{
  "abstract": "Background Immune checkpoint blockades have emerged as major therapies for patients with lung adenocarcinoma. However, there may still be a group of patients with advanced metastasis have not benefited from it, and the median overall survival for patients remains less than 3 years. Identifying the factors affecting the efficacy of immune checkpoint blockades and targeting the beneficiaries accurately become important clinical issues.Methods Clinical significance of SUSD2 was assessed in TCGA cohorts. SUSD2 function was determined in syngeneic tumors and humanized mice. Flow cytometry and cytokine array panel were used to further revealed immune cells infiltration in allografts. Co-IP and immunofluorescence were used to identified SUSD2 targets.Results SUSD2 expression in patients who benefited from anti-PD-1 antibodies was significantly higher than that in patients with disease progression ( figure 1A-B), and it was positively correlated with the overall survival of patients with lung adenocarcinoma in TCGA-LUAD (figure 1C-D). Knockdown of SUSD2 significantly promoted tumor growth and induced immunosuppressive microenvironment in LLC syngeneic tumors (figure 1E-H). FASC identified increased infiltration of myeloid-derived suppressor cells (MDSCs), accompanied by reduced infiltration of CD4+ and CD8+ T cells in SUSD2 knockdown tumors (figure 1I-L). Cytokine array panel and RT-qPCR and Western blot showed that knocking down SUSD2 in lung adenocarcinoma cells led to increased CXCL1 expression and secretion (figure 2A-C). CO-IP and immunofluorescence revealed TRAF2 as a SUSD2 target (figure 2D-F). SUSD2 competes with TRADD for TRAF2 binding (figure 2G-H), to upregulate CXCL1 by activate TNF/NF-κB signaling, thereby suppressing MDSCs migration.Conclusions SUSD2 boosts antitumor immunity via a TRAF2/NF-κB/CXCL1 axis to inhibited LUAD.Abstract 449 Figure 1SUSD2 functions as a suppressor of LUAD progression by modulating the immune microenvironmentAbstract 449 Figure 2Low SUSD2 expression promotes CXCL1 secretion by activate TNF/NF-kB signaling",
  "authors": [
    {
      "affiliations": [
        "Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China"
      ],
      "name": "Zhen Cheng"
    },
    {
      "affiliations": [
        "Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China"
      ],
      "name": "Huihao Lu"
    },
    {
      "affiliations": [
        "Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China"
      ],
      "name": "Chuhong Huang"
    },
    {
      "affiliations": [
        "Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China"
      ],
      "name": "Wenmei Su"
    }
  ],
  "title": "449 SUSD2 augments antitumor immunity by targeting TRAF2/NF-κB/CXCL1 axis in lung adenocarcinoma",
  "uid": "7290683a-0fdc-51f0-8c53-c73f366c16cc"
}