Impact of mild hyperthermia on tumor-immune dynamics explored through mathematical modeling

The immune system plays a vital role in cancer control, yet its efficacy is often compromised by tumor-induced immunosuppression. Moderate hyperthermia ([Formula: see text]C) can enhance immune responses and improve therapeutic outcomes. This work investigates how mild hyperthermia modulates tumor-immune dynamics through a mathematical modeling approach. Specifically, we analyze how heat-induced reduction in tumor proliferation and enhancement of immune recruitment affect tumor control outcomes. We extend the Kuznetsov model of tumor-immune interactions by incorporating thermal effects on two key parameters: tumor growth rate and immune cell recruitment rate. A bifurcation analysis is performed to characterize how the system's equilibrium structure changes as these parameters vary. Our analysis shows that the tumor-immune system has critical points where small changes in tumor growth or immune response can dramatically alter outcomes. Moderate hyperthermia can shift these tipping points in favor of the immune system, making it more likely that the tumor is controlled rather than escapes immune surveillance. In practical terms, hyperthermia expands the conditions under which immune-mediated tumor suppression is successful and reduces the scenarios that would lead to tumor progression, effectively improving the chances of therapeutic control. These results provide quantitative insight into how transient hyperthermia can reshape tumor-immune dynamics, increasing the likelihood of immune-mediated tumor suppression. The model suggests that moderate hyperthermia, by simultaneously reducing tumor proliferation and enhancing immune recruitment, can shift tumor-immune interactions toward control in a subset of initial conditions. Thus, it offers a theoretical framework supporting the use of hyperthermia as an immunomodulatory adjuvant in cancer therapy, particularly in combination with immunotherapeutic strategies.