Oncolytic viruses and immunotherapy: the perfect match

We are used to considering viruses as enemies, tending to forget the multitude of their other applications in biotechnology and biomedicine. For one thing, did you know that viruses could be weapons against cancer cells? In fact, that is precisely what oncolytic viruses are used for. Moreover, a review recently published on Nature Immunology explores their possible combination with other anti-neoplastic agents and especially with cancer immunotherapy. Viruses and immune system: two sworn enemies that somehow work “together” against tumour cells.

An oncolytic virus is a virus that preferentially infects cancer cells, where it replicates its viral particles and finally causes the cell lysis. Some viruses naturally exhibit a tropism for tumour cells, which in most cases lack a functional antiviral response making life much easier for their host. Nevertheless, sometimes researchers use “tricks” to force the virus to replicate only in the tumor. For example, the virus external proteic shell, which is called “capsid”, can be modified to enhance its binding to receptors exclusively expressed on the surface of tumour cells or viral genes can be placed under the control of other genetic sequences called “promoters” that promote the expression of such genes only in cancer cells.

However, we cannot speak of viruses or cancer without considering the fundamental role of the immune system: what is the connection between these three components?

Immune cells do not only protect us from external agents, but also recognize and kill cancer cells: if such “immune surveillance” worked perfectly, there would be no tumours at all, but unfortunately, people continue to get sick. In fact, the naturally occurring immune response against cancer cells is often “switched off” in the tumour microenvironment. Cancer immunotherapy aims to restore such response; nevertheless, only those patients with a high density of functional lymphocytes infiltrating the tumour are likely to benefit from the treatment.

Here oncolytic viruses come into play, potentiating antitumor immunity through various mechanisms. When the infected cell dies, it expresses some molecules on its surface that recruit the components of the immune system like macrophages and dendritic cells, which phagocyte the dying cells: this is called “immunogenic cell death” and promotes the awakening of immune response. Moreover, the virus-mediated lysis of the tumour cells releases additional soluble molecules, which expands the repertoire of tumour-specific antigens that become potential targets for lymphocytes. In addition, as viral antigens are potent immunogens, oncolytic viruses are also associated with initiation of both innate and adaptive immunity, recruitment of lymphocytes within the tumour and most importantly maintenance of their effector phenotype: indeed, with the “help” of oncolytic viruses the tumour-mediated immune suppression is partially reversed.

Many scientists think that the future of cancer treatment is the combination therapy. This makes sense, as cancer is not a single disease, but a multiform and versatile enemy and we must be just as multifaceted and versatile to defeat it. Combination therapies allow to attack cancer on multiple fronts while strengthening each other at the same time. Both oncolytic viruses and cancer immunotherapy work on patients and now researchers think that it is time to combine them into a more potent treatment.

Erika salvatori

Reference:
Bommareddy, P.K., et al. (2018). Integrating oncolyitic viruses in combination cancer immunotherapy. Nature Reviews Immunology.

This article is also available in Italian