SexImmunome of Virus-assisted Cancer Immunotherapy: Discovery, Characterization and Therapeutic Implications

Similar to what you would read in sci-fi novels, viruses can be used to treat human malignancies. On October 27, 2015, the US Food and Drug Administration (FDA) approved the use of herpes virus (trade name Imlygic) for the treatment of skin cancer. This first-of-a-kind historic decision is set to accelerate the already fast-paced research and development efforts around similar type of therapeutics. These cancer-killing viruses, known as oncolytic viruses (OVs), act through two distinct mechanisms: 1) kill cancer cells directly, and 2) educate patient's immune system to attack cancer on its own. It is now clear that these virus-driven anti-tumor immune responses are the indispensable part of this therapy. Currently, many viruses are being tested in clinical trials worldwide for the treatment of cancers of almost every origin. These virus-assisted cancer immunotherapies (VaCIs) are believed to be one of the most promising cancer treatments of the modern era. Interestingly, no preclinical research to this date has investigated the impact of sex on VaCIs. Unfortunately, these findings from preclinical research done without considering sex as a variable get further extended in clinical settings and continue to be applied in a generalized fashion between sexes. It is now evident that these practices form the basis of differential therapeutic efficacies/toxicities between males and females. Evidence suggests that sex influences host immune responses, especially in the context of virus infection and cancer patho-physiology. This evidence has led to the hypothesis that sex-biased differences must exist between males and females during VaCIs. Hence, the overarching goal of this preclinical research project is to first understand the sex-biased immunological differences (collectively designated as SexImmunome), and then define their impact on the efficacy of virus-based cancer immunotherapy.