Background: According to previous clinical trials and pilot studies, PD1 antibodies might provide favorable long-term survival in combination with chemotherapy for unresectable hepatobiliary and pancreatic (HBP) cancers. We conducted a real-world evaluation of PD1 antibodies in patients with unresectable HBP cancers. We also aimed to explore biomarkers for the early prediction of PD1 antibodies response. Methods: From Jan 2021 to Dec 2021, 48 unresectable HBP cancers were enrolled in Yuhang campus, the first affiliated hospital, Zhejiang university school of medicine. The key eligibility criteria were:(1)histopathologically confirmed advances unresectable HBP cancers; (2)without systematic treatment; (3)¡Ý18 years old; (4)ECOG PS 0 or 1. Clinical decisions were made by multi-disciplinary team (MDT). The treatment efficacy was evaluated by mRECIST. Results: A total of 48 patients were finally included and analyzed, which their baseline characteristics were listed in Table. we assessed the treatment efficacy using the dynamic change of tumor makers. And we observed that tumor markers of progressive disease(PD) group were higher than those of stable disease(SD) and partial response(PR) group. A total of 37 patients with complete biomarker data, were finally included in cytokines and immune response analysis. During the immune checkpoint inhibitors treatment, we detect the trough concentration of serum cytokines(IL-2, IL-4, IL-6, IL-10, IL-16, TNF-¦Á and TIFN-¦Ã). We observed that serum cytokines indexes of PD group were higher than those of SD and PR group. Conclusions: We observed that tumor markers of PD group were higher than those of SD and PR group. The serum cytokines (IL-4, IL-16 and TIFN-¦Ã) may be potential biomarkers for the early prediction of PD1 antibodies response.