Tackling HLA Deficiencies Head on with Oncolytic Viruses

SIMPLE SUMMARY: Oncolytic viruses show great promise as anticancer agents by simultaneously lysing cancer cells while stimulating innate and adaptive immune responses. However, the extent to which the adaptive immune system contributes to overall efficacy alongside oncolytic viruses is, in part, dependent on the compliance of cancer cells to present antigens correctly. Dysregulation of any part of the antigen presentation machinery provides a strong selection pressure for immune escape. In this review, we consider the key immunological factors that might be measured to allow for the optimum deployment of oncolytic viruses for effective cancer therapy. ABSTRACT: Dysregulation of HLA (human leukocyte antigen) function is increasingly recognized as a common escape mechanism for cancers subject to the pressures exerted by immunosurveillance or immunotherapeutic interventions. Oncolytic viruses have the potential to counter this resistance by upregulating HLA expression or encouraging an HLA-independent immunological responses. However, to achieve the best therapeutic outcomes, a prospective understanding of the HLA phenotype of cancer patients is required to match them to the characteristics of different oncolytic strategies. Here, we consider the spectrum of immune competence observed in clinical disease and discuss how it can be best addressed using this novel and powerful treatment approach.