Thermalization of Cold Tumor: A Comprehensive Treatment Path for the Transformation of Cold Tumor to Hot Tumor

This article reviews the emerging comprehensive treatment strategies for the transformation of "cold tumor" to "hot tumor", aiming to overcome the limitations of immunotherapy in tumors with low response rates. "Hot tumors" usually have abundant immune cell infiltration and active immune microenvironment, while "cold tumors" respond poorly to immunotherapy due to less immune cell infiltration and strong inhibitory microenvironment. This article focuses on three TME remodeling strategies: Tesla Cell activates innate immunity through metabolic reprogramming (such as inhibition of LDH-A and neutralization of lactate); Near-infrared photoimmunotherapy (NIR- PIT) uses photosensitizers to induce immunogenic death and reverse the immunosuppressive microenvironment. Hyperthermia enhances the activity of immune cells by directly killing tumor cells with high temperature and releasing antigens. In addition, this article analyzes the potential of these strategies in combination with immune checkpoint inhibitors, adoptive cell therapy and tumor vaccines, and compares their intrinsic/exogenous characteristics, safety and clinical transformation prospects. The "hyperthermia" of cold tumors provides a new direction for immunotherapy, which is expected to significantly improve the efficacy of refractory tumors.