Jia Liu

A Replication-Defective Myxoma Virus Inducing Pro-Inflammatory Responses as Monotherapy and an Adjuvant to Chemo- and DC Immuno-Therapy for Ovarian Cancer

Myxoma virus (MYXV), a rabbit-specific poxvirus and non-pathogenic in humans and mice, is an excellent candidate oncolytic virus for cancer therapy. MYXV also has immunotherapeutic benefits. In ovarian cancer (OC), immunosuppressive tumor-associated macrophages (TAMs) are key to inhibiting antitumor immunity while hindering therapeutic benefit by chemotherapy and dendritic cell (DC) vaccine. Because MYXV favors binding/entry of macrophages/monocytes, we examined the therapeutic potential of MYXV against TAMs. We found previously that a replication-defective MYXV with targeted deletion of an essential gene, M062R, designated ΔM062R MYXV, activated both the host DNA sensing pathway and the SAMD9 pathway. Treatment with ΔM062R confers therapeutic benefit comparable to that of wild-type replicating MYXV in preclinical models. Here we found that ΔM062R MYXV, when integrated with cisplatin and DC immunotherapy, further improved treatment benefit, likely through promoting tumor antigen-specific T cell function. Moreover, we also tested ΔM062R MYXV in targeting human immunosuppressive TAMs from OC patient ascites in a co-culture system. We found that ΔM062R treatment subverted the immunosuppressive properties of TAMs and elevated the avidity of cytokine production in tumor antigen-specific CD4+ T cells. Overall, ΔM062R presents a promising immunotherapeutic platform as a beneficial adjuvant to chemotherapy and DC vaccine.

The Association between Five Genetic Variants in MicroRNAs (rs2910164, rs11614913, rs3746444, rs11134527, and rs531564) and Cervical Cancer Risk: A Meta‐Analysis

The objective of this study was to conduct a meta‐analysis to systematically summarize and investigate the association of miRNA‐124 rs531564, miRNA‐218 rs11134527, miRNA‐146a rs2910164, miRNA‐196a2 rs11614913, and miRNA‐499 rs3746444 polymorphisms with cervical cancer. A systematic review was performed to identify relevant studies using Embase and PubMed databases. A chi‐square‐based Q‐test combined with the inconsistency index (I2) was used to check the heterogeneity between studies. A total of six case‐control studies on rs2910164 and rs11614913, 4 studies on rs3746444 and rs11134527, and three studies on rs531564 were included. No evidence of association was found between miR‐146a rs2910164, miR‐196a2 rs11614913, miRNA‐499 rs3746444, and miR‐218 rs11134527 polymorphisms and cervical cancer risk in all the genetic models. The miR‐124 rs531564 polymorphism was associated with a statistically increased risk of cervical cancer in a homozygote model (CC vs. GG: OR = 2.87, 95% CI: 1.40‐5.91, PH = 0.887), dominant model (GC/CC vs. GG: OR = 1.38, 95% CI: 1.07‐1.80, PH = 0.409), and recessive model (CC vs. GC/GG: OR = 2.26, 95% CI: 1.58‐3.23, PH = 0.979). However, this finding should be interpreted with caution for limited samples and heterogeneity. Large‐scale and well‐designed studies are needed to validate our result.