Viroimmunotherapy of Thoracic Cancers

Abstract

Thoracic cancers, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and malignant pleural mesothelioma (MM), cause the highest rate of cancer mortality worldwide. Most of these deaths are as a result of NSCLC; however, prognoses for the other two diseases remain as some of the poorest of any cancers. Recent advances in immunotherapy, specifically immune checkpoint inhibitors, have begun to help a small population of patients with advanced lung cancer. People who respond to these immune therapies generally have a durable response and many see dramatic decreases in their disease. However, response to immune therapies remains relatively low. Therefore, intense research is now underway to rationally develop combination therapies to expand the range of patients who will respond to and benefit from immune therapy. One promising approach is with oncolytic viruses. These oncolytic viruses (OVs) have been found to be selective for or have been engineered to preferentially infect and kill cancer cells. In pre-clinical models of different thoracic cancers, it has been found that these viruses can induce immunogenic cell death, increase the number of immune mediators brought into the tumor microenvironment and broaden the neoantigen-specific T cell response. We will review here the literature regarding the application of virotherapy toward augmenting immune responses in thoracic cancers.

Keywords: immune infiltration; immunogenic cell death; immunotherapy; lung cancer; mesothelioma; oncolytic virus; thoracic cancers; viroimmunotherapy.

Figure 1

Schematic representation of possible mechanisms by which oncolytic virotherapy can exert immunologic effects in the tumor microenvironment. Initial viral infection of the tumor cell leads to viral replication and lysis. Progeny virions then can infect and lyse surrounding cells amplifying tumor lysis. This infection can then directly lead to release of damage associated and pathogen associated molecular patterns (DAMP and PAMP, respectively) as well as interferons into the tumor microenvironment. These can further attract T cells, decrease suppressive cells, and lead to upregulation of programmed death ligand (PDL-1) on tumor cells promoting antitumor immunity.