Scientists have reported that increased tumor oxygenation occurred after heating at mild temperature in rodent tumors. Several studies support that local heating (40-43°C) results in an overall improvement of tumor oxygenation. The changes in tumor oxygenation after heating correlated with changes of tumor blood flow. The increase of oxygen delivery into the tumor through increased blood flow after heating could reduce hypoxic regions within the tumor micro-environment. However, a higher thermal dose (>43°C) leads to decrease of tumor oxygenation possibly because of blood vessel damage.
Thermal therapy can be used to relieve, at least temporarily, the grip of hypoxia in the tumor micro-environment through its effects on vascular function. Heat-induced changes in blood flow (from exercise, fever, or changes in ambient temperature) is due to controlled amounts of both vasoconstriction and vasodilation of blood vessels. Hyperthermia results in an obvious expansion in the diameters of many tumor blood vessels and an increase in the percentage of perfused blood vessels with discernible erythrocytes.
“Mild thermal therapy may have a dual benefit: direct enhancement of immune cell activity through thermally sensitive molecular pathways associated with immune cell function/activation, and, indirect enhancement of immunosurveillance through a reduction in hypoxia-induced immune suppression via improved tumor vascular perfusion.
Hypoxia not only helps tumor cells to escape recognition of cytolytic cells (e.g., by inducing shedding of targets for NK cells) but also prevents the proper maturation and function of dendritic cells and T lymphocytes and increases the potential for recruitment of immunosuppressive T lymphocytes and tumor associated macrophages.
Mild, fever-range systemic hyperthermia can significantly increase the percentage of perfused blood vessels within tumors and that this effect can last for hours. Moreover, systemic heating is associated with a significant depression in interstitial fluid pressure. Other recent research has also revealed that exposure of immune cells and tumor cells to mild hyperthermia have positive effects on the same immune mechanisms that are negatively impacted by hypoxia.