Comparing thermal stress reduction strategies that influence MDSC accumulation in tumor bearing mice
Cameron MacDonald1, Samuel Ministero1, Manu Pandey2
1Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States.
Abstract:
Myeloid derived suppressor cells (MDSCs) are a diverse collection of immune cells that suppress anti-tumor immune responses. Decreasing MDSCs accumulation in the tumor microenvironment could improve the anti-tumor immune response and improve immunotherapy. Here, we examine the impact of physiologically relevant thermal treatments on the accumulation of MDSCs in tumors in mice. We found that different temperature-based protocols, including 1) weekly whole-body hyperthermia, 2) housing mice at their thermoneutral temperature (TT, ~30 °C), and 3) housing mice at a subthermoneutral temperature (ST,~22 °C) while providing a localized heat source, each resulted in a reduction in MDSC accumulation and improved tumor growth control compared to control mice housed at ST, which is the standard, mandated housing temperature for laboratory mice. Additionally, we found that low dose β-adrenergic receptor blocker (propranolol) therapy reduced MDSC accumulation and improved tumor growth control to a similar degree as the models that relieved cold stress. These results show that thermal treatments can decrease MDSC accumulation and tumor growth comparable to propranolol therapy.
Insights
Thermal treatments, including hyperthermia and thermoneutral housing, reduce myeloid-derived suppressor cells (MDSCs) in tumors. This approach improves anti-tumor immunity and tumor growth control, similar to propranolol therapy.
Area of Science:
- Immunology
- Cancer Biology
- Therapeutic Hypothermia
Background:
- Myeloid-derived suppressor cells (MDSCs) are key regulators of anti-tumor immunity.
- MDSC accumulation in the tumor microenvironment impairs effective anti-cancer immune responses and immunotherapy outcomes.
- Targeting MDSCs represents a promising strategy to enhance cancer treatment efficacy.
Purpose of the Study:
- To investigate the impact of physiologically relevant thermal treatments on MDSC accumulation in a mouse tumor model.
- To compare the efficacy of different thermal protocols and propranolol therapy in modulating MDSCs and tumor growth.
Main Methods:
- Mice bearing tumors were subjected to various thermal conditions: weekly whole-body hyperthermia, housing at thermoneutral temperature (~30°C), or housing at subthermoneutral temperature (~22°C) with localized heating.
- Control mice were housed at subthermoneutral temperature (22°C).
- MDSC levels in tumors and tumor growth were assessed. Low-dose propranolol therapy was also evaluated.
Main Results:
- All tested thermal treatment protocols (hyperthermia, thermoneutral housing, localized heating) significantly reduced MDSC accumulation in tumors.
- These thermal interventions led to improved tumor growth control compared to standard housing conditions.
- Low-dose propranolol therapy demonstrated comparable reductions in MDSCs and tumor growth, highlighting the potential of non-pharmacological interventions.
Conclusions:
- Physiologically relevant thermal treatments effectively decrease MDSC accumulation within the tumor microenvironment.
- Thermal strategies offer a promising avenue for enhancing anti-tumor immune responses and improving cancer immunotherapy.
- Temperature modulation presents a viable alternative or adjunct to pharmacological approaches like propranolol for cancer treatment.
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