Among the three primary gynecological malignancies, ovarian cancer has the lowest incidence but the worst prognosis. Because of the poor prognosis of ovarian cancer patients treated with existing treatments, immunotherapy is emerging as a potentially ideal alternative to surgery, chemotherapy, and targeted therapy. Among immunotherapies, immune checkpoint inhibitors have been the most thoroughly studied, and many drugs have been successfully used in the clinic. CD47, a novel immune checkpoint, provides insights into ovarian cancer immunotherapy. This review highlights the mechanisms of tumor immune evasion via CD47-mediated inhibition of phagocytosis and provides a comprehensive insight into the progress of the relevant targeted agents in ovarian cancer.
Relapsed/refractory ovarian cancer, especially platinum resistance recurrence, remains a major therapeutic challenge. Here, we present the case of a patient with recurrent ovarian clear cell carcinoma (OCCC) who failed to respond to multiline chemotherapy and target therapy but achieved an immune complete response (iCR) with programmed cell death 1 (PD-1) inhibitor treatment. The overall survival (OS) was 59 months, and the recurrence-free survival (RFS) was 34 months after immunotherapy, which was counting. Meantime, molecular testing results revealed that traditional biomarkers for immunotherapy, including PD-L1 expression, microsatellite instability (MSI), and tumor mutational burden (TMB), were negative. HLA-B44 (B*18:01) supertype was confirmed by sequence-based HLA typing. This case raises the possibility that ovarian cancer patients with multidrug resistance may still benefit from PD-1 inhibitor therapy, even if PD-L1 pathology is negative.
Endometriosis is a chronic inflammatory disease. The immune-checkpoint molecules CD226 and TIGIT play an important role in regulating T cells' function. However, little is known about the proportion and function of CD226 and TIGIT on CD4 + T cells in endometriosis. The current study found no significant differences in the TIGIT percentage on peripheral CD4 + T cells between patients with endometriosis and the control group. However, CD226 was lower in patients with endometriosis than that in the control group (P < 0.01). The cytokines TNF-α, IL10, and IFN-γ were significantly elevated in TIGIT + CD4 + T cells compared to TIGIT-CD4 + T cells. HLA-DR + cells were more numerous among TIGIT + CD4 + T cells than among the TIGIT-subset (P <0.001). Similarly, the cytokines TNF-α, IL10, and IFN-γ were significantly elevated in CD226 + CD4 + T cells compared to levels in CD226-CD4 + T cells. The proportion of HLA-DR + CD4 + T cells among CD226 + CD4 + T cells was also significantly higher than that among the CD226-subset (P < 0.001). After TIGIT was blocked, the level of IL-10 in TIGIT + CD4 + T cells was higher than that in cells with unblocked TIGIT. There were no differences in TNF-α and IFN-γ. After CD226 was blocked, TNF-α and IFN-γ were lower while IL-10 was higher. In conclusion, there is a diminution of CD226 in CD4 + T cells in patients with endometriosis. This is correlated with the effector function of CD4 + T cells, and blocking CD226 can suppress this function.
Background
Primary debulking surgery (PDS) or neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) was the standard treatment for advanced ovarian cancer. Optimal cytoreduction is believed one of the most important factors for survival. However, in patients with extra-abdominal metastases which is impossible to achieve optimal cytoreduction around whole body, which treatment should be used is not clear yet.
Methods
Patients with stage IV epithelial ovarian cancer with extra-abdominal metastases who underwent primary treatment between January 1, 2015 and January 31, 2022 were identified. Data were retrospectively extracted. Each patient record was evaluated to subclassify stage IV disease according to the sites of metastases at the time of diagnosis. Kaplan-Meier plot and Log-rank test were used to analyze the difference between two groups. Univariate and multivariate Cox regression analysis were used to identify important prognostic factors.
Results
A total of 72 newly diagnosed stage IV epithelial ovarian cancer patients were included, in which 36 (50%) patients underwent PDS, 36 (50%) patients underwent NACT-IDS. The median overall survival was significantly longer in PDS group than NACT-IDS group (51.3 months vs. 36 months, p = 0.027). Patients receiving PDS has significantly longer progression-free survival than who received NACT-IDS (21.6 months vs. 14.3 months, p = 0.049). The rate of no residual disease was higher in patients with NACT-IDS versus PDS (61% vs. 44%). The complete response rate was significantly higher in PDS group than NACT group (83% vs. 67%, p = 0.013) after PDS/IDS and full course of chemotherapy. Women who received PDS had a trend toward a higher rate of grade III/IV postoperative complications than those who received NACT (25% vs. 6%, p = 0.046).
Conclusions.
PDS for epithelial ovarian cancer patients with extra-abdominal metastasis resulted in longer OS and PFS than NACT + IDS. Cytoreduction to no residual disease in the interval debulking surgery should be the goal in patients who receive NACT.
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