Inclusion Criteria:
* Signed written informed consent prior to any study-related procedures;
* Male or female, aged ≥ 18 years;
* Cohort 1: Histologically confirmed gastric or gastroesophageal junction adenocarcinoma, locally advanced per AJCC 8th edition, cTNM stage cT2-4N+M0 by endoscopic ultrasound or contrast-enhanced CT/MRI (with endoscopic ultrasonography and diagnostic laparoscopic exploration if necessary), and assessed as resectable by the investigator;
* Cohort 2: Histopathologically confirmed unresectable advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, cTNM stage cT4bN+M0/1 by endoscopic ultrasound or contrast-enhanced CT/MRI (with endoscopic ultrasonography and diagnostic laparoscopic exploration if necessary) (M1 defined as presence of distant metastasis, including but not limited to oligometastasis and extensive metastasis);
* No prior systemic treatment for the current disease, including surgery, antitumor radiotherapy/chemotherapy/immunotherapy;
* MSI-H by microsatellite instability testing (using the 5 microsatellite loci recommended by the National Cancer Institute: BAT25, BAT26, NR21, NR24, NR27, or other guideline- and clinically-recognized locus combinations) or dMMR by mismatch repair testing (expression of the 4 common MMR proteins MLH1, MSH2, MSH6, and PMS2 by immunohistochemistry, with positive expression localized in the nucleus);
* Agreement to undergo radical surgery and no surgical contraindications as judged by the surgeon (Cohort 1);
* ECOG performance status 0-1;
* No serious concomitant diseases threatening survival (expected survival time \< 5 years);
* Adequate organ function, meeting the following laboratory criteria: Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count ≥ 90×10⁹/L; hemoglobin \> 80 g/L; Total bilirubin ≤ 1.5×ULN (≤ 3×ULN for participants with Gilbert's syndrome or liver metastasis); if total bilirubin \> 1.5×ULN or 3×ULN but direct bilirubin ≤ ULN, enrollment also permitted; AST and ALT ≤ 2.5×ULN (≤ 5.0×ULN for patients with liver metastasis); Serum creatinine ≤ 1.5×ULN and creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min; Good coagulation function, defined as INR or PT ≤ 1.5×ULN; certain anticoagulants (e.g., antiplatelet agents, vitamin K antagonists) discontinued 7-14 days before surgery and replaced with other drugs (e.g., low molecular weight heparin);
* At least one measurable lesion per RECIST v1.1;
* For women of childbearing potential, negative urine or serum pregnancy test within 3 days before first dose of study drug (Day 1 of Cycle 1); serum pregnancy test required if urine result cannot be confirmed as negative; non-childbearing potential defined as at least 1 year postmenopausal, or surgical sterilization or hysterectomy;
* For all participants (male or female) with risk of conception, contraceptive measures with an annual failure rate \< 1% throughout treatment until 120 days after last dose of study drug (or 180 days after last dose of chemotherapy).
Exclusion Criteria:
* Prior receipt of any antitumor therapy for the study disease, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy;
* Prior receipt of anti-PD-1, anti-PD-L1, anti-programmed death ligand 2 (PD-L2), or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) agents, or any other agents acting on T-cell costimulatory or immune checkpoint pathways (e.g., OX40, CD137, etc.), or adoptive cell immunotherapy;
* Concurrent participation in another clinical study, unless participating in an observational (non-interventional) clinical study or in the survival follow-up phase of an interventional study;
* Receipt of any investigational drug or investigational device therapy within 4 weeks before the first dose of study drug;
* Major surgery (e.g., craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose of study drug, anticipated need for major surgery during the study treatment period (except radical gastrectomy specified in the protocol), or presence of unhealed wounds, ulcers, or fractures; exploratory surgery for tumor staging is permitted;
* Use of immunosuppressive drugs within 4 weeks before the first dose of study drug, excluding: Intranasal inhaled local steroid therapy or local steroid injection (e.g., intra-articular injection); Systemic corticosteroid therapy not exceeding 10 mg/day prednisone or its equivalent physiological dose; Corticosteroids as prophylaxis for allergic reactions (e.g., premedication before CT);
* Receipt of Chinese patent medicine with antitumor indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukin, excluding local use for control of pleural effusion) as systemic treatment within 2 weeks before the first dose;
* Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years before the first dose; replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic treatment;
* History of other primary malignancies, excluding: Cured malignancy with no known active disease and very low risk of recurrence ≥ 2 years before the first dose of study drug; Adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease recurrence; Adequately treated carcinoma in situ with no evidence of disease recurrence;
* Human immunodeficiency virus (HIV) infection (HIV antibody positive);
* Acute or chronic active hepatitis B (defined as HBsAg positive, or HBcAb positive alone with HBV DNA ≥ 2000 IU/mL or ≥ 1×10⁴ copies/mL), or acute or chronic active hepatitis C (defined as HCV antibody positive with HCV-RNA level above the lower limit of detection);
* Known history of primary immunodeficiency;
* Interstitial lung disease requiring treatment; prior or current pulmonary diseases such as pulmonary fibrosis, pneumoconiosis, drug-related pneumonia, organic pneumonia (e.g., bronchiolitis obliterans), or severe impairment of pulmonary function;
* Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
* Presence of any serious or uncontrolled systemic disease, such as: Resting electrocardiogram showing major and severe symptomatic uncontrolled abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmia, or atrial fibrillation with poorly controlled ventricular rate (ventricular rate \> 110 beats/min); Poorly controlled unstable angina, congestive heart failure, or chronic heart failure of New York Heart Association (NYHA) class ≥ 2; History of deep vein thrombosis, pulmonary embolism, cerebral infarction, or any other serious thromboembolic event within 3 months before the first dose of study drug (implantable venous access port or catheter-related thrombosis, or superficial vein thrombosis is not considered a "serious" thromboembolic event); Poorly controlled blood pressure (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg); Active pulmonary tuberculosis; Active or uncontrolled infection requiring systemic treatment; Severe bleeding tendency or coagulation disorder, or currently receiving thrombolytic therapy; Presence of gastrointestinal obstruction; Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; Poorly controlled diabetes (fasting blood glucose (FBG) \> 10 mmol/L); Urine protein ≥ 3+ on urinalysis, with confirmed 24-hour urinary protein \> 1.0 g; Presence of psychiatric disorders preventing cooperation with treatment;
* Known allergy to the drugs used in this study;
* Pregnant or breastfeeding women;
* History or evidence of disease, treatment, or abnormal laboratory values that may interfere with study results, prevent full participation in the study, or any other condition considered unsuitable for enrollment by the investigator; presence of other potential risks considered unsuitable for participation in this study by the investigator.
