The key "accomplice" of drug resistance in gastric cancer was found to have individualized treatment or joint targets

2022-02-25

Professor Xu jiejie from the school of basic medicine of Fudan University found in a large sample and multicenter study involving 795 patients with gastric cancer that interleukin-1 receptor 1 (il-1r1), a molecule previously considered to play a key role in chronic inflammation, plays a key "accomplice" role in inducing local immunosuppression and therapeutic resistance of gastric cancer. At the same time, the study found for the first time that there is a close relationship between the expression level of il-1r1 molecule and the treatment response of patients, so it can be used as a new cofactor to guide the individualized treatment of gastric cancer patients and a potential target of combined therapy. Relevant papers were recently published in the latest issue of the international academic journal "Journal of tumor immunotherapy". Xu jiejie introduced that gastric cancer is a highly heterogeneous tumor, and there are great individual differences between different patients. Therefore, only by taking individualized and accurate treatment can we achieve the best effect. At present, the evaluation of postoperative survival, the prediction of chemotherapy response and the choice of treatment for patients insensitive to chemotherapy are three difficult problems for clinicians. In recent years, the rise of immunotherapy provides a new strategy for the treatment of patients with gastric cancer. However, only 20% of patients apply this therapy effectively. Further analysis of tumor microenvironment and focus on the function of key molecules are urgent problems to be solved in the treatment of gastric cancer. The research of Xu jiejie's scientific research team found that the high-level expression of "accomplice" il-1r1 molecule in gastric cancer participated in the "Recruitment" of macrophages related to tumor deterioration, inhibited immunity, and weakened the anti-tumor immune response of CD8 + T cells in the microenvironment of gastric cancer; Pabolizumab, an inhibitor of immune checkpoints targeting CD8 + T cells, has no effect on patients with high expression of il-1r1, that is, il-1r1 promotes drug resistance of gastric cancer by mediating immune escape of gastric cancer. At the same time, the effect of chemotherapeutic drugs not only depends on the direct killing of cancer cells, but also depends on the reactivation of immune cells to help sweep away the residual cancer cells. Patients with high expression of il-1r1 are also insensitive to adjuvant chemotherapy due to the lack of "knife mending" effect of immune system. Therefore, the response of patients to immune checkpoint inhibitor pabolizumab and chemotherapy drugs can be judged by detecting the expression level of il-1r1 in tissue samples of patients with gastric cancer. (outlook new era)

Edit:Yuanqi Tang    Responsible editor:Xiao Yu

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