Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that exhibit immunosuppressive activity. They also directly stimulate tumor cell proliferation, metastasis, and angiogenesis. In ovarian cancer, there are increased numbers of circulating or tumor-infiltrating MDSCs, and increased frequencies of MDSCs are associated with a poor prognosis or an advanced clinical stage. Moreover, in murine models of ovarian cancer, MDSC depletion has shown significant growth-inhibitory effects and enhanced the therapeutic efficacy of existing anticancer therapies. In this review, we summarize the current knowledge on MDSC biology, clinical significance of MDSC, and potential MDSC-targeting strategies in ovarian cancer.

Uterine cervical and endometrial cancers are the two most common gynecological malignancies. As demonstrated in other types of solid malignancies, an increased number of circulating or tumor-infiltrating myeloid-derived suppressor cells (MDSCs) have also been observed in uterine cervical and endometrial cancers, and increased MDSCs are associated with an advanced stage, a short survival, or a poor response to chemotherapy or radiotherapy. In murine models of uterine cervical and endometrial cancers, MDSCs have been shown to play important roles in the progression of cancer. In this review, we have introduced the definition of MDSCs and their functions, discussed the roles of MDSCs in uterine cervical and endometrial cancer progression, and reviewed treatment strategies targeting MDSCs, which may exhibit growth-inhibitory effects and enhance the efficacy of existing anticancer treatments.

The interactions between platelets and cancer cells activate platelets and enhance tumor growth. Platelets increase proliferation and epithelial–mesenchymal transition in cancer cells, inhibit anoikis, enhance the extravasation of cancer cells, and protect circulating tumor cells against natural killer cells. Here, we have identified another mechanism by which platelets dampen the immune attack on cancer cells. We found that platelets can blunt the antitumor immune response by increasing the expression of inhibitory immune checkpoint (PD-L1) on ovarian cancer cells in vitro and in vivo. Platelets increased PD-L1 in cancer cells via contact-dependent (through NF-κB signaling) and contact-independent (through TFGβR1/Smad signaling) pathways. Inhibition of NF-κB or TGFβR1 signaling in ovarian cancer cells abrogated platelet-induced PD-L1 expression. Reducing platelet counts or inhibiting platelet functions reduced the expression of PD-L1 in ovarian cancer. On the other hand, an increase in platelet counts increased the expression of PD-L1 in tumor-bearing mice.

Several studies have investigated the potential effects of hyponatremia on recurrent febrile seizures (RFS) during febrile illness. Because findings were inconsistent across studies, we aimed to evaluate the serum sodium levels in febrile seizures (FS) of children with or without RFS during the same episode. We conducted electronic searches in three databases (PubMed, EMBASE, Cochrane Library) and one scholarly search engine (Google Scholar) up to June 2021 for studies on FS. Screening was done based on the titles and abstracts of primary studies. Then, eligibility was reviewed based on the abstracts. Finally, in order to match the inclusion and exclusion criteria, full-text articles were evaluated by two authors and inconsistencies were discussed. Data extraction was carried out by two independent authors. The extracted variables were author's name, article title, journal name, year of publication, study location, study design, sample size, and mean and standard deviation of blood Na concentration in FS. We performed a risk of bias assessment of included studies using the Newcastle-Ottawa Scale (NOS). The effect size was calculated using the standardized mean difference (SMD), and random-effects models were used for the analysis. A total of 12 articles were included with a single outlier. This analysis suggested that serum sodium level was lower in patients with RFS during the same febrile episode than in those with single FS, with SMD of -0.70, (n=1784; 95% CI: -1.03, -0.36; Z=-4.10, p<0.01; I² 86.67%, p<0.01). In the sensitivity analysis, no significant change was observed in pooled SMD. The optimal cutoff value of serum sodium level was 134.72 mmol/L with an area under the receiver operating characteristic curve of 0.81 (95% CI: 0.61, 1.00), with sensitivity of 80.0% and specificity of 70.0%. This result indicated a significant association between hyponatremia and RFS during the same febrile episode. Decreased serum sodium levels may be involved in seizure recurrence and may play a role in FS pathogenesis.

We and other investigators have shown that platelets promote metastasis and the growth of tumors. Our rationale for conducting this study is that platelets’ prometastatic and progrowth effects depend on a close encounter between platelets and cancer cells. This interaction occurs inside blood vessels with circulating tumor cells and outside blood vessels with cancer cells residing in the tumor parenchyma. Our hypothesis was that platelet extravasation is required for the effect of platelets on tumor growth. Platelets respond to environmental stimuli by activation of G protein–coupled receptors on their surface. We investigated the impact of various platelet G proteins on the growth of ovarian cancer tumors and platelet extravasation. We used mice with platelet-specific deficiency of Gαi2 (Gi), Gα13 (G13), or Gαq (Gq) in a syngeneic ovarian cancer model. We measured the total weight of tumor nodules resected from tumor-bearing mice. We developed methods for automated whole-slide image acquisition and unbiased computerized image analysis to quantify extravasated platelets. We compared the number of platelets inside tumor nodules of platelet G protein–deficient tumor-bearing mice. We found that deficiency of Gi and G13, but not Gq, in platelets resulted in smaller tumors compared with those in corresponding littermates. Deficiency of Gi and G13 in platelets reduced the number of extravasated platelets by >90%, but deficiency of Gq did not reduce the number of extravasated platelets significantly. The lack of Gi or G13 in platelets reduced platelet extravasation into the tumor and tumor growth.