Looking for biomarkers in interferon response pathway to predict response to oncolytic HSV-1 in breast cancer: An ex vivo study

Abstract

Breast cancer is the most common malignancy in women worldwide. Administration of oncolytic viruses is one of the novel promising cancer therapy approaches. Replication of these viruses is usually limited to cancer cells that have interferon (IFN) signaling defects. However, Interferon signaling is not completely impaired in all cancer cells which may limit the benefits of virotherapy. Identification of realistic IFN-mediated biomarkers to identify patients who most likely respond to virotherapy would be helpful. In this study, eight patients-derived primary tumor cultures were infected with an ICP34.5 deleted oHSV, then the rate of infectivity, cell survival, and expression of the gene involved in IFN pathway were analyzed. Data showed that mRNA expressions of Myeloid differentiation primary response protein (Myd88) is significantly higher in tumors whose primary cultures showed less cell death and resistance to oHSV infectivity (P-value < 0.05). The differentiating cut off of Myd88 expression, inferred from the receiver operating characteristic (ROC) curve, predicted that only 13 out of 16 other patients could be sensitive to this oHSV. Identifying such biomarker improves our ability to select the patients who do not exhibit resistance to virotherapy.

New hopes for the breast cancer treatment: perspectives on the oncolytic virus therapy

“…Genetic signatures linked to viral replication, immune response pathways, or susceptibility to viral infection might also contribute to predicting response to OVs in breast cancer. An example of this approach is the identification of realistic interferon (IFN)-mediated biomarkers to identify patients who most likely respond to virotherapy ( 123 ) as replication of OV is usually limited to cancer cells that have interferon (IFN) signalling defects. Upregulation of protein biomarkers such as IFN gamma may reflect immune induction and become an OV efficacy biomarker to improve the ability to select patients who do not exhibit resistance to virotherapy ( 124 ).…”

The VISTA/VSIG3/PSGL-1 axis: crosstalk between immune effector cells and cancer cells in invasive ductal breast carcinoma

“…Therefore, they can aid in the early detection of cancer, even before the appearance of symptoms. Early identification is frequently associated with better treatment results and greater survival rates [5,[10][11][12][13][14][15].…”