Weihong Zhao

Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity

AbstractBackgroundPeripheral blood‐derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic effector function of PBNK cells and improving NK cell expansion in vitro for a convenient allogeneic therapy are essential.Materials and MethodsPure cytokine activation and expansion of NK cells (super NK [SNK]) from peripheral blood mononuclear cells were studied. Markers of activated and inhibited NK cells and cytokine secretion by NK cells were examined using flow cytometry. NK cell antitumor activity in vitro was assessed using lactate dehydrogenase (LDH) cytotoxicity assay and an Incucyte real‐time imaging system. Additionally, the function of SNK cells against ascites caused by ovarian cancer in NOD‐Prkdc(em26Cd52)il2rg(em26Cd22)/Nju (NCG) mice was determined. In a further investigation of the differences between PBNK and SNK, the mRNA of both cells was sequenced and analyzed.ResultsHuman peripheral blood mononuclear cells showed selective NK cell expansion upon cytokine activation and culture. Both SNK and PBNK cells expressed activation markers, but at different levels, and SNK cells secreted more cytokines related to cytotoxicity than PBNK cells did. Accordingly, SNK cells exhibited strong antitumor activity ex vivo and improved NCG mice survival after intraperitoneal ovarian cancer transplantation. Mechanistically, SNK cells expressed more genes associated with nucleotide metabolism, fatty acid, and ATP metabolism than PBNK cells.ConclusionSNK cells derived from peripheral blood mononuclear cells have sufficiently activated mature characteristics and high antitumor activity, rendering them a highly promising and essential therapeutic approach for cancer treatment.

Prevalence, genotype distribution and risk factors of cervical HPV infection in Yangqu, China: a population-based survey of 10086 women

Human papillomavirus(HPV) infection is a necessary factor for the development of cervical cancer. The HPV vaccine is currently available, but there is still a lack of large-scale research on the distribution and risk factors of HPV. The aim of this study is to investigate the genotype distribution and risk factors of HPV infection in Yangqu which is located in North China. This study enrolled 10086 women aged <65 years from Yangqu County. HPV genotypes were identified via standard HPV DNA testing. The overall prevalence of HPV infection was 8.92%. The prevalence of high-risk HPV types was 8.80%, and it was 0.38% for low-risk HPV types. Single genotype infection accounted for 67.91% in HPV-positive cases. The most common HPV genotypes were HPV-16, -52, and -58. HPV-18 was only the 11th most common type in HPV-positive cases. Women ≥50 years of age had the highest prevalence rate of HPV, and women <30 years had the lowest prevalence rate. The distribution of HPV genotypes also varied among the three age groups: <30, 30-49, and ≥50 years. The risk factors that contributed to the rate of HPV infection included low educational level, low income, smoking, age at first sexual encounter <23 years old, and number of births ≥3 times. This large routine clinical practice report of HPV prevalence and genotype distribution revealed the characteristics of HPV infection-type distributions in Shanxi Province, which should be considered in formulating comprehensive prevention strategies including vaccination for cervical cancer in China.