{
  "abstract": "Background Mismatch repair deficiency (dMMR) colorectal cancer (CRC) is characterized by abundant tumor-infiltrating lymphocytes and tertiary lymphoid structures (TLSs). However, while B cells are pivotal for TLS formation, their function and the signaling pathways driving their activation in dMMR CRCs remain undefined.Methods Data from The Cancer Genome Atlas (TCGA) database analyzed by XCELL method and multiplex immunofluorescence (MIF) staining tissue slides were used to compare the abundance and distribution of TLSs and B cell populations between dMMR and proficient MMR cohorts. Then MLH1 knockdown models both in vitro and in vivo were used to mimic dMMR/high microsatellite instability (MSI-H) tumors and explore the influence of tumor cells on B cell behavior.Results TCGA analysis and MIF staining revealed a significant association between memory B cell abundance, TLS formation, and improved prognosis in dMMR CRCs. In vivo MLH1 knockdown models showed that B cell depletion enhanced tumor growth and reduced the efficacy of anti-PD-1 treatment in dMMR CRCs. Furthermore, in vitro experiments demonstrated a dsDNA/STING/type I interferon (IFN)/STAT1/ ccl19 signaling pathway mediating the dMMR-induced increase in memory B cells.Conclusions In conclusion, these findings show that CCL19 generated by STING/type I IFN/STAT1 pathway in dMMR/MSI-H CRC cells can promote the expansion of memory B cells, which suppresses tumor growth and enhances the efficacy of PD-1 blockade.",
  "authors": [
    {
      "affiliations": [
        "Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China",
        "Fuzhou University Affiliated Provincial Hospital",
        "School of Medicine,Fuzhou University, Fuzhou, Fujian, China"
      ],
      "name": "Huilin Huang"
    },
    {
      "affiliations": [
        "Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China",
        "Zhongshan City People’s Hospital, Zhongshan, Guangdong, China"
      ],
      "name": "Zhian Chen"
    },
    {
      "affiliations": [
        "Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xinyuan Mao"
    },
    {
      "affiliations": [
        "Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Jiaqiang Jiang"
    },
    {
      "affiliations": [
        "Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yijie Xi"
    },
    {
      "affiliations": [
        "Peking University Shenzhen Graduate School, Shenzhen, Guangdong, China",
        "Shenzhen Bay Laboratory, Shenzhen, Guangdong, China"
      ],
      "name": "Yihong Wan"
    },
    {
      "affiliations": [
        "Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Lingzhi Wang"
    },
    {
      "affiliations": [
        "Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xinhua Chen"
    },
    {
      "affiliations": [
        "Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yanfeng Hu"
    }
  ],
  "title": "Memory B cell subset shapes antitumor immunity and response to PD-1 blockade in mismatch repair-deficient colorectal cancers",
  "uid": "e3816d49-4016-5548-9131-7df687fdcaa8"
}