Introduction
Gastric cancer, tumor, gastric cancer
GASTRIC CANCER, TUMOR PROGRESSION, TUMOR, GASTRIC CANCER
Gastric cancer remains a major killer globally, ranking fifth for incidence and fourth for mortalityRecently, immune checkpoint inhibitors (ICIs) achieved superior outcomes to placebo in the third-line treatment for advanced gastric cancer in phase III randomized controlled trialsTumor angiogenesis plays an essential role in tumor progression. Like ICIs, antiangiogenic agents target tumor microenvironment (TME) components other than tumor cells and synergize with ICIs by promoting CD8In this phase II trial, we explore the efficacy and safety of a neoadjuvant/conventional combination therapy with anti-PD1 antibody (camrelizumab), antiangiogenic agent (apatinib), and chemotherapy (S-1 ± Oxaliplatin) in stage T4a/bN+M0 gastric cancer patients. Complete and major pathological response rates are 15.8% and 26.3%. Sequential multi-omics tests, including whole-exome sequencing (WES), transcriptome sequencing, and T cell receptor (TCR) sequencing, reveal several putative biomarkers for pathological responses and dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy.