Study Evaluating Neoadjuvant Immunotherapy Increasing CD8+ Cell Infiltration in Advance Gastric Adenocarcinoma

Inclusion Criteria:

1. Age from 18 to 75 years
2. Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically ；
3. CT/MRI, PET-CT, or laparoscopic exploration should be performed before surgery to confirm the diagnosis of stage ≥cT2 or N+；
4. Patients who have not received other treatments such as surgery, radiotherapy, chemotherapy, targeted therapy or immunotherapy；
5. Performance status of 0 or 2 on Eastern Cooperative Oncology Group scale (ECOG)；
6. Estimated survival time was over 3 months；
7. No serious heart, lung and liver dysfunction; no jaundice and gastrointestinal obstruction; no acute infection;；
8. The major organs are functioning normally and meet the following criteria:

(1) Blood routine examination should meet the requirements (no blood transfusion within 14 days):

1. HB≥100g/L，
2. WBC≥3×109/L
3. ANC≥1.5×109/L，
4. PLT≥100×109/L； （2）Biochemical tests must meet the following criteria：

a. BIL \<1.5×upper limit of normal (ULN)， b. ALT and AST\<2.5ULN，GPT≤1.5×ULN； c. Cr≤1ULN，Ccr \>60ml/min 9. Fertile women must have taken a pregnancy test (serum) within 7 days prior to enrollment with negative results and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last trial drug; For men, they should be surgically sterilized or agree to use the appropriate method of contraception during the trial period and 8 weeks after the last administration of the trial drug 10. Did not participate in other clinical studies before and during treatment 11. Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up

Exclusion Criteria:

1. History of other malignant disease within past five years；
2. History of immunodeficiency, including HIV positive, or other acquired congenital immunodeficiency disease, or a history of organ transplantation and allogeneic bone marrow transplantation；
3. Contraindications to surgery and chemotherapy, or whose physical condition and organ function do not allow for major abdominal surgery
4. Distant metastases；
5. Accompanied by severe heart, lung, liver and kidney diseases; neurological and mental diseases; jaundice and accompanied by severe infection；
6. Women during pregnancy or breast-feeding；
7. Patients with high blood pressure that cannot be reduced to the normal range after antihypertensive drug treatment (systolic blood pressure\>140 mmHg, diastolic blood pressure\>90 mmHg);
8. Suffering from coronary heart disease of grade I or above, arrhythmia (including QTc interval prolongation \> 450 ms in men and \> 470 ms in women), and cardiac insufficiency;
9. Patients with a clear tendency to gastrointestinal bleeding, including the following conditions: patients with locally active ulcer lesions, fecal occult blood (++), and history of melena and hematemesis within 2 months; patients with abnormal coagulation function (INR\> 1.5, APTT\>1.5 ULN);
10. Patients with a history of cardiovascular and cerebrovascular diseases who are still taking oral thrombolytics or anticoagulants;
11. Patients with positive urine protein (urinary protein test 2+ or above, or 24-hour urine protein quantitative\> 1.0g;
12. Multiple factors affect oral drugs (such as inability to swallow, persistent uncontrollable nausea and vomiting, chronic diarrhea and intestinal obstruction, etc.);
13. Those who have allergic reactions to the drugs in this study;
14. The researcher believes that it is not suitable for inclusion.