Tumor Temperature: Friend or Foe of Virus-Based Cancer Immunotherapy

Abstract

The temperature of a solid tumor is often dissimilar to baseline body temperature and, compared to healthy tissues, may be elevated, reduced, or a mix of both. The temperature of a tumor is dependent on metabolic activity and vascularization and can change due to tumor progression, treatment, or cancer type. Despite the need to function optimally within temperature-variable tumors, oncolytic viruses (OVs) are primarily tested at 37 °C in vitro. Furthermore, animal species utilized to test oncolytic viruses, such as mice, dogs, cats, and non-human primates, poorly recapitulate the temperature profile of humans. In this review, we discuss the importance of temperature as a variable for OV immunotherapy of solid tumors. Accumulating evidence supports that the temperature sensitivity of OVs lies on a spectrum, with some OVs likely hindered but others enhanced by elevated temperatures. We suggest that in vitro temperature sensitivity screening be performed for all OVs destined for the clinic to identify potential hinderances or benefits with regard to elevated temperature. Furthermore, we provide recommendations for the clinical use of temperature and OVs.

Keywords: cancer; oncolytic virus; solid tumor; temperature.

Figure 1

The effects of oncolytic virus (OV) therapy and physiological changes on tumor temperature. OV therapy can increase tumor temperature by (A) causing fevers in recipients and (B) inducing antitumor immune responses, which increase inflammation and heat generation. OV therapy can also decrease tumor temperature by (C) destroying tumor vasculature and (D) causing direct oncolysis of tumor cells, which increases the number of necrotic regions. Physiological changes can also impact tumor temperature. Physiological changes such as (E) increased tumor vasculature and (F) increased metabolic activity of tumor cells can contribute to increases in tumor temperature. (G) Tumor cells have also been shown to overexpress procoagulants which can cause intravascular thrombosis, decreasing tumor temperature due to hypoxia, necrosis, and reduced metabolic activity of tumor cells.