Hypoxia effects on oncolytic virotherapy in Cancer: Friend or Foe?

Researchers have tried to find novel strategies for cancer treatment in the past decades. Among the utilized methods, administering oncolytic viruses (OVs) alone or combined with other anticancer therapeutic approaches has had promising outcomes, especially in solid tumors. Infecting the tumor cells by these viruses can lead to direct lysis or induction of immune responses. However, the immunosuppressive tumor microenvironment (TME) is considered a significant challenge for oncolytic virotherapy in treating cancer. Based on OV type, hypoxic conditions in the TME can accelerate or repress virus replication. Therefore, genetic manipulation of OVs or other molecular modifications to reduce hypoxia can induce antitumor responses. Moreover, using OVs with tumor lysis capability in the hypoxic TME may be an attractive strategy to overcome the limitations of the therapy. This review summarizes the latest information available in the field of cancer virotherapy and discusses the dual effect of hypoxia on different types of OVs to optimize available related therapeutic methods.

Association of HScore Parameters with Severe COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Several reports have associated the severe Coronavirus disease-2019 (sCOVID-19) with secondary-hemophagocytic lymphohistiocytosis (sHLH) and proposed utilizing the hemophagocytic syndrome diagnostic score (HScore) for sCOVID-19 patients. We conducted a systematic review and meta-analysis to find the possible association of HScore parameters with severity in COVID-19 patients. METHODS: A systematic search was performed in Medline via PubMed, EMBASE, and Cochrane databases using all HScore and COVID-19 keywords. The studies were all from 2020, and the study language was limited to English. The records were screened based on inclusion/exclusion criteria. Random/fixed-effect models were employed for meta-analysis, based on the I2 index of parameters. The pooled mean differences were estimated for continuous parameters. The pooled odds-ratio was estimated for fever. The level of significance was set at 0.05. RESULTS: Eighteen studies (comprising 2459 patients) out of 26151 screened studies were included in this meta-analysis. The results showed that the level of leukocyte, neutrophil, aspartate transaminase (AST), ferritin, and fibrinogen were significantly higher in sCOVID-19 patients than in non-severe ones. Significant lower levels of lymphocyte, platelet, and hemoglobin were also found in sCOVID-19 patients than non-severe patients. Fever was nearly associated with two times increased odds of sCOVID-19 (P=0.051). CONCLUSION: Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, high levels of AST, and fever are common features of both sCOVID-19 and HLH. However, the leukocytosis, neutrophilia, and hyperfibrinogenemia found in sCOVID-19 are in contrast with HScore. Conclusively, HScore parameters could be risk factors for sCOVID-19. However, some parameters' roles are contradictory, suggesting the need for further investigation and a new way of HScore interpretation in sCOVID-19 patients.A preprint of this study was published at https://www.researchsquare.com/article/rs-54490/v2.