Carboplatin and programmed death-ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model.

In advanced, platinum resistant or refractory ovarian cancer (OC), the therapeutic efficacy of carboplatin is controversial. Although anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway blockages show great potential in cancer treatment, the antitumor effect of single anti-PD-L1 pathway monoclonal antibody (mAb) is not obvious in advanced or some poorly immunogenic tumors, including OC. We compared the effects of single or combined carboplatin and anti-PD-L1 mAb treatments and explored the possible antitumor mechanisms in a murine ID8 OC model. C57BL/6 mice with established peritoneal ID8 OC were intraperitoneally injected with single or combined carboplatin and anti-PD-L1 mAb. The formation time of ascites and their overall survival were recorded. The compositions of tumor-associated immune cells were analyzed by flow cytometry. A single treatment of carboplatin and combined carboplatin/PD-L1 mAb induced a strong anti-ascites response. Mice treated with carboplatin presented the longest overall survival, followed by the combined remedy. Mechanistic investigation of the tumor microenvironment revealed that carboplatin and carboplatin/PD-L1 mAb increased antitumor effector CD4+ , CD8+ T cells and decreased immunosuppressive regulatory T and myeloid suppressor cells, giving rise to remarkably higher ratios of effector CD4+ , CD8+ T cells to regulatory T cells and myeloid suppressor cells in the peritoneal cavity. To our knowledge, this is the first report to compare the antitumor effect and potential mechanisms between carboplatin, PD-L1 mAb and their combination strategies in a murine ID8 OC model. The results of this study may deepen our understanding of OC and aid future preclinical experiments or clinical trials.

Zhu X ，Xu J ，Cai H ，Lang J ... -  《-》

Combined Trabectedin and anti-PD1 antibody produces a synergistic antitumor effect in a murine model of ovarian cancer.

Guo Z ，Wang H ，Meng F ，Li J ，Zhang S ... -  《Journal of Translational Medicine》

Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs.

Lu L ，Xu X ，Zhang B ，Zhang R ，Ji H ，Wang X ... -  《Journal of Translational Medicine》

PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer.

Guo Z ，Wang X ，Cheng D ，Xia Z ，Luan M ，Zhang S ... -  《PLoS One》

Programmed death-1 pathway blockade produces a synergistic antitumor effect: combined application in ovarian cancer.

Programmed death-1 (PD-1) and its ligand are part of the immune checkpoint pathway that down-regulates effector T cells in immune response, thereby causing immune suppression. The PD-1/programmed death-ligand 1 (PD-L1) pathway can be blocked by antibodies to reverse tumor-mediated immunosuppression. However, advanced cancers such as stage III-IV ovarian cancer (OC) and certain types such as ID8 OC (a clone of C57BL/6 mouse OC) may hijack the PD-1/PD-L1 pathway to escape immune attack. When combined with chemotherapy, radiotherapy, targeted therapy, immunotherapy, or other agents, these PD-1/PD-L1 pathway blockages can produce a synergistic antitumor response in OC. Combined immunotherapy significantly prolongs overall survival by changing the tumor microenvironment through processes such as increasing the number of CD4⁺ or CD8⁺ T cells or cytokines in mice with OC and decreasing the number of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). OC patients treated with combined immunotherapy received better prognoses than those treated with monotherapy. This review reflects the move toward novel therapy combinations for OC and discusses these promising immunotherapeutic approaches, which are more cost-effective and effective than other approaches.

Zhu X ，Lang J 《-》