e16099 Background: Neoadjuvant chemotherapy (NAC) is still the main strategy for operable local advanced gastric cancer (GC) or gastroesophageal junction cancer (EGJ). Keynote585 and Matterhorn studies had demonstrated the improvement of pathologic complete response rate (PCR), however, the overall survival benefit remains unclear. Little is known why patients’ response differently to NAC in terms of chemotherapy regiment and post neoadjuvant tumor microenvironment (TME). Methods: We retrospectively analyzed the resectable GC or EGJ patients who had been treated with neoadjuvant chemotherapy followed by surgery during 2019.11.26-2023.8.18 in the Chinese PLA general hospital. Patients with complete survival data were enrolled in the final evaluation. The association between clinical features or chemotherapy regiment and outcomes including TGR grade (NCCN criteria) and survival data were explored. Furthermore, tumor-microenvironment by means of multiplex fluorescence staining(mIHC) (CD8, CD68, CD56, PD1, PDL1, PANCK) after SOX neoadjuvant chemotherapy was analyzed. Results: 184 patients were offered neoadjuvant chemotherapy and underwent surgery. Due to follow-up lost, 141 patients with complete survival data were included in this analysis finally. Average age was 61, majority of patients were male. 85 patients received Sox and 33 received Xelox and 12 patients with docetaxel and S1(DS) and 11 patients were administered with triplets (FOLT and DOS). The median cycle of neoadjuvant treatment was 4(range from 1-7). Large proportion of patients were performed Laparoscopic. 31 patients suffered from post surgery complication. Above all, 1-year DFS and 2-year DFS, 3-year DFS rate were 72.6%, 54.8%, 49.0% respectively. 2-year OS and 3-year OS rate were 76.9%, 64.5%. PCR rate was 6.38% (n=9), which is consistent with other previous studies. 9 patients achieved TRG 0 and 26 had TRG 1. There is no statistical difference between triplets and double regiment of NEC for TRG0-1 group (45.5% vs 23.1%, p=0.099). The addition of docetaxel to oxaliplatin based therapy had not improved the TRG0-1 population compared with docetaxel-free regiment (30.4% VS 23.7%, p=0.496). YN0 is a predictor of longer survival in contrast YN+( 1-year DFS, 89.4% vs 62.8%, p=0.000).In the mIHC analyses, the density of CD8 positive and CD8+PD1- in the TGR0-1 group is higher than those cells in the TGR 2-3 group(P<0.05). TGR0-1 group had lower density of PDL1+,CD68+PDL1+ and CD68+PDL1- cells in contrast to TGR 2-3 group(P<0.05).Other multi-dimensional analyses were ongoing to be further disclosure. Conclusions: Neoadjuvant chemotherapy led to nearly 7% PCR rate for patients with local advanced GC. YN0 after NAC is a predictor of longer survival. CD8 positive and CD8+PD1- might be the determinant immune cells for better anticancer-response when exposed to chemotherapy.