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Programmed cell death-1 (PD-1) immune checkpoint inhibitors have exhibited promising efficacy in various types of tumors. Here, we report an unresectable locally advanced gastric cancer (GC) with programmed cell death ligand-1 (PD-L1) positive and microsatellite instability (MSI), which exhibiting an unexpected efficacy of pathological complete response (pCR) after a single dose of anti-PD-1 therapy in combination with chemotherapy as a first-line setting. A 66-year-old man diagnosed with gastric cancer and was clinically staged as cT4aN+M0. After one cycle treatment (oxaliplatin plus capecitabine plus anti-PD-1antibody), repeated computed tomography (CT) showed tumor shrinkage and the plasma carcinoembryonic antigen decreased dramatically. Curative distal gastrectomy with D2+ lymphadenectomy was performed and the pathological staging was pT0N0M0. Immunohistochemistry and polymerase chain reaction-based method revealed that the patient had a PD-L1 positive and MSI-high GC, while the Epstein-Barr virus was absent. Furthermore, much CD8 + tumor-infiltrating lymphocytes (TILs) were observed within the tumor and invasion front, which were responsible for tumor shrinkage, due to the recognition of abundant tumor neoantigens and their corresponding immune checkpoints. Our case report indicates that a combination of immunotherapy plus chemotherapy as a first-line treatment might offer a promising treatment option for locally advanced gastric adenocarcinoma with PD-L1 positive and MSI-high.

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&lt;p&gt;Pathological Complete Response After a Single Dose of Anti-PD-1 Therapy in Combination with Chemotherapy as a First-Line Setting in an Unresectable Locally Advanced Gastric Cancer with PD-L1 Positive and Microsatellite Instability&lt;/p&gt;