For advanced gastric cancer, standard treatment is D2 gastrectomy combined with perioperative medications, when the tumor is infiltrating into submucosa, around or with lymph node metastasis, and can reduce the success rate of surgery, previous studies have showed a tumor on perioperative chemotherapy helps to drop period, and improve the long-term survival of patients, compared with surgery alone, It can improve the 5-year overall survival (OS) by about 10%. At present, SOX protocol is recommended as the perioperative protocol for advanced gastric cancer in domestic guidelines [5]. However, for patients with T3/T4 or positive lymph node (N+), the probability of recurrence or metastasis after resection is high, and the 5-year survival rate is only 23%. Previous studies have found that the prognosis of patients with complete pathological response or near complete pathological response after neoadjuvant chemotherapy is significantly improved, whereas the pCR rate is only less than 10%. It is an effective way to improve the prognosis of gastric cancer patients to seek neoadjuvant therapy that can improve the pathological response rate. Chemotherapy and immune checkpoint inhibitor drugs have a synergistic mechanism on the theoretical basis. Pd-1 inhibitors are a kind of immune checkpoint inhibitors. In the process of immune escape of tumors,PD-1 inhibitors are involved in the activation process of the immune system, and by inhibiting PD-1 receptors, T cells can be activated normally. Thus, the immune system of the body can promote the killing of tumor cells.~Our research group plans to carry out the study of carrelizumab (PD-1) combined with SOX/XELOX chemotherapy as a neoadjuvant therapy in locally advanced gastric cancer. A total of 34 patients with locally advanced gastric or gastroesophageal junction carcinoma of T3-4NXM0 were enrolled. After 3 cycles of carrelizumab (PD-1) combined with chemotherapy, radical resection was performed, and the treatment effect was evaluated by pathological remission of the surgical tissue. Collection and treatment of gastroscope biopsy tissue samples before and after neoadjuvant therapy surgery samples: 1. The multiple fluorescent immunohistochemical (mIHC) technique were used to detect the immune cells in tumor tissue infiltration, compared neoadjuvant therapy after curative effect before treatment between patients with good and poor effects of immune cell infiltration, the difference between a explore treatment response and the correlation between the baseline immune microenvironment; To compare the changes of immune cell infiltration before and after treatment, and to explore the effect of combined immunotherapy on the immune microenvironment of locally advanced gastric cancer. 2. High-throughput sequencing technology was used to sequence DNA molecules to compare the pre-treatment gene sequences between patients with good and poor efficacy after neoadjuvant therapy, and to explore the correlation between the effect of neoadjuvant therapy and gene sequence changes (dMMR, MSI, TMB, PD-L1, etc.).
This is a single-arm, open, exploratory clinical study to evaluate the efficacy of carrelizumab (PD-1) combined with chemotherapy (SOX/XELOX) as neoadjuvant therapy and to observe the changes of tumor immune microenvironment in patients with locally advanced gastric or gastroesophageal junction cancer (T3-4NXM0).