An important role for granulocytes in the thermal regulation of colon tumor growth
ABSTRACT
Several lines of research show that cells of the immune response are sensitive to thermal variations in their microenvironment, such as that which occurs during inflammation and fever; these data have led to the hypothesis that strategic applications of heat could assist in controlling tumor growth in animal models. The innate immune response is known to play a critical role in the development of effective anti-tumor immunity and granulocytes such as polymorphonuclear neutrophils (PMNs), as key mediators of inflammation, have been suggested to have the potential to initiate immune response cascades against tumors. Thus, we hypothesized that PMNs may play a crucial role in mediating the anti-tumor effects of a mild, fever-range whole-body hyperthermia (FR-WBH) protocol, where core body temperatures are raised to 39.5-40 degrees C for 8 hrs. Indeed, in BALB/c mice bearing the colon tumor CT26, the anti-tumor effect of WBH correlates with increased granulocytic infiltrate at the tumor site as determined using immunohistochemical analysis for Gr-1+ cells. In both BALB/c mice bearing CT26 and SCID mice bearing human colon tumors, PMN depletion in vivo using anti-Gr-1 ascites ablated the anti-tumor effect of mild WBH. Because mild thermal stress is also found to enhance the respiratory burst of granulocytes, these data collectively suggest that the thermal stimulation of granulocytes may help to prevent tumor establishment. Overall, these results may have implications for the design of thermal therapy protocols in cancer immunotherapy.