Background
Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer.
Methods
A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions.
Results
We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5.
Conclusions
PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.
Background: Assessing the humoral immune response to SARS-CoV-2 is crucial for inferring protective immunity from reinfection and for assessing vaccine efficacy. Data regarding the durability and sustainability of SARS-CoV-2 antibodies are conflicting. In this study, we aimed to determine the seroconversion rate of SARS-CoV-2 infection in a cohort of reverse-transcriptase polymerase chain reaction (RT–PCR)-confirmed SARS-CoV-2 infections and the antibody dynamics, durability, and the correlation of antibody titers with disease severity using the commercially available SARS-CoV-2 anti-spike (S1/S2) protein.Methods: A total of 342 subjects with PCR-confirmed COVID-19 were enrolled. A total of 395 samples were collected at different time points (0–204) after the onset of symptoms or from the day of positive PCR in asymptomatic patients. Demographics, clinical presentation and the date of PCR were collected. All samples were tested using the automated commercial chemiluminescent system (DiaSorin SARS-CoV-2 S1/S2 IgG) on the LIAISONXL® platform (LIAISON).Results: The seroconversion rate for samples collected 14 days after the onset of infection was much higher than that for samples collected before 14 days (79.4% vs. 39.4%). The rate of seroconversion in symptomatic participants (62.1%) was similar to that of asymptomatic participants (56.1%) (p = 0.496). The IgG titer distribution was also similar across both groups (p = 0.142), with a median IgG level of 27.86 AU/ml (3.8–85.5) and 15 AU/ml (3.8–58.85) in symptomatic and asymptomatic participants, respectively. However, IgG titers were significantly higher in ICU patients, with a median of 104 AU/ml (3.8–179) compared to 34 AU/ml (3.8–70) in the non-ICU participants (p < 0.0001). Furthermore, the median time to seroconversion occurred significantly faster in ICU patients than in non-ICU participants (19 versus 47 days) (P < 0.0001). IgG titers were also higher in subjects ≥50 years compared to those <50 years (p < 0.009), male compared to female (p < 0.054) and non-Saudi compared to Saudi (p < 0.003). Approximately 74% of all samples tested beyond 120 days were positive.Conclusion: Antibodies can persist in circulation for longer than 4 months after COVID-19 infection. The majority of patients with COVID-19 mounted humoral immune responses to SARS-CoV-2 infection that strongly correlated with disease severity, older age and male gender. However, the population of individuals who tested negative should be further evaluated.
In adult tissue, the paired box 2 (PAX2) protein is expressed in healthy oviductal, but not normal ovarian surface epithelial cells. PAX2 is expressed in a subset of cases of serous ovarian carcinoma; however, the role of PAX2 in the initiation and progression of ovarian cancer remains unknown. The aim of the present study was to determine the biological effects of PAX2 expression in normal and cancerous epithelial cells. By culturing the normal and cancerous ovarian cells that express PAX2 in 3D culture and staining the cells with vasculogenic mimicry markers such as CD31 and PAS, it was shown that PAX2 overexpression in both normal and cancerous ovarian epithelial cells induced formation of vascular-like structures both in vitro and in vivo. These results indicated a potential role of PAX2 in ovarian cancer progression by increasing the presence of vascular-like structures to promote the supply of nutrients to tumor cells and facilitate cancer cell proliferation and invasion.
Background
Graft‐versus‐host disease (GVHD) is a rare but serious complication after pediatric liver transplantation (LTx). Early diagnosis is difficult due to nonspecific presenting symptoms and non‐pathognomonic skin histopathological features. The aim of this article was to describe a case of pediatric GVHD after LTx and to review available data on pediatric GVHD highlighting the diagnostic difficulty. We also propose a diagnostic algorithm to improve the diagnostic capability and increase clinical awareness about this potentially fatal condition.
Methods
We did a comprehensive literatures review on studies on GvHD following pediatric LTx between 1990 and February 2021, chimerism study by short tandem repeat (STR), HLA typing by sequence‐specific oligonucleotide (SSO) method, and flowcytometry crossmatch.
Results
Our search yielded 23 case reports. The most common clinical manifestations were fever and rash (91%) followed by diarrhea. Mortality rate was 36.8% mainly due to sepsis and organ failure. Diagnosis was challenging and chimerism study to confirm donor engraftment was performed on only half of the cases. Prevalence of “donor dominant HLA one‐way matching” typically occurs in homozygous parents‐to‐child transplantation was 75% in cases with HLA testing.
Conclusion
So far, there are no available standard diagnostic criteria for GVHD following pediatric LTx. Recognition of multiple risk factors through proper laboratory assessment can predict the occurrence, and early chimerism study can confirm suggestive clinical manifestation. The strong likelihood of developing GVHD in “donor one‐way HLA match” and the severe problems imposed by this complication may justify avoidance of HLA homozygous parent's donation.
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