Thermal Reprogramming of the Tumor Immune Microenvironment: From Molecular Mechanisms to Clinical Translation

Hyperthermia, defined as the controlled elevation of tissue temperature in the range of 39–45 °C, is increasingly recognized as a potent modulator of tumor biology and anti-tumor immunity. Beyond its established role as a sensitizer to radiotherapy and chemotherapy, hyperthermia induces profound molecular and cellular changes within the tumor microenvironment (TME), promoting immunogenic cell death and reshaping immune composition and function.At the molecular level, thermal stress activates conserved stress response pathways, including the induction of heat shock proteins (HSPs), protein denaturation, and the release of damage-associated molecular patterns (DAMPs) and neoantigens. These events enhance antigen processing and presentation, stimulate dendritic cell activation, and promote priming and expansion of tumor-specific T cell responses. Concurrently, hyperthermia influences vascular permeability, perfusion, and metabolic constraints within the TME, thereby modulating immune cell trafficking and function.Despite these advances, a comprehensive and mechanistic understanding of how hyperthermia reprograms the tumor–immune ecosystem remains incomplete. In particular, the causal signaling networks, spatial organization, and dynamic cellular interactions that underpin heat-induced anti-tumor immunity are not fully elucidated.Recent developments in high-dimensional and functional approaches -including single-cell and spatial multi-omics, high-parameter cytometry, and perturbation-based platforms- now enable systematic dissection of these processes with unprecedented resolution. Integration of these technologies with in situ and functional validation provides new opportunities to define the molecular circuits and cellular states that govern thermal reprogramming of the TME.This Research Topic aims to advance mechanistic insight into how hyperthermia shapes both local and systemic anti-tumor immune responses. We particularly encourage studies that:- Elucidate causal molecular pathways and signaling networks driving heat-induced immune activation or suppression- Define spatial and cellular dynamics of immune remodeling within the TME using single-cell and spatial approaches- Identify and functionally validate biomarkers associated with response or resistance to hyperthermia- Leverage experimental models (e.g., organoids, co-culture systems, in vivo perturbation) to establish mechanistic causality- Provide mechanistically grounded frameworks for integrating hyperthermia with existing therapeutic modalitiesBy bridging molecular mechanisms with functional and spatial biology, this Research Topic seeks to establish hyperthermia as a powerful experimental and therapeutic framework to interrogate and modulate tumor–immune interactions.Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this Research Topic. Topic editors: Shuvojit Moulik, Alak Manna, Sanchaita Misra Source: https://www.frontiersin.org/research-topics/82978/thermal-reprogramming-of-the-tumor-immune-microenvironment-from-molecular-mechanisms-to-clinical-translation