The AURELIA trial demonstrated that adding
Bevacizumab to
chemotherapy significantly improved progression-free survival (PFS) for
platinum resistant recurrent
ovarian cancer. Recently,
immunotherapy also presented potential anti-
tumor effects in several malignant solid
tumors. This study aimed to investigate whether combining anti-PD-L1
Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in
cisplatin resistant
epithelial ovarian cancer (CREOC). We retrospectively analyzed 124
epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with
cisplatin resistance due to progressing <6 months after completing
platinum-based
therapy. Based on responding to at least 2 cycles of
Bevacizumab-containing
chemotherapy (BC), these Patients were divided into BC response group and BC non-response group. Immunohistochemistry was used to detect that PD-L1 expression and
tumor angiogenesis-related
proteins (
VEGF and Semaphorin4D) in tissues from 124 patients with CREOC. The positive expressions of PD-L1,
VEGF, and Semaphorin4D (
SEMA4D) were found in 58.73, 50.79, and 71.43% of the 63 cases CREOC tissues with BC response, respectively, which were significantly higher than that in the 61 cases BC non-response group (P < 0.05). PD-L1 expression correlated with
SEMA4D and
VEGF positively (r = 0.344 and 0.363, P < 0.001). Over-expressions of PD-L1,
VEGF and
SEMA4D are associated with more malignant clinicopathologic characteristics of CREOC Patients. In survival analysis, patients' response to BC was the independent factor for evaluation of PFS and overall survival (OS). Cell functional assays showed that
Atezolizumab in combination with
Bevacizumab inhibited the proliferation, migration, and invasion of
cisplatin resistant
ovarian cancer cell line A2780cis in vitro synergistically, which maybe associate with
Bevacizumab suppressing the epithelial-mesenchymal transition (EMT) and PD-L1 expression by targeting STAT3. Furthermore,
Bevacizumab and
Atezolizumab induced synergistic anti-
tumor effect in vivo. These findings suggest a novel therapeutic strategy for
cisplatin resistant recurrent EOC and its mechanism warrants further study.