Metabolic reprogramming is a malignancy hallmark, which refers to the ability of cancer cells to alter metabolic and nutrient acquisition modes in order to support the energy demands for accomplishing the rapid growth, dissemination, metastasis and obtain the "building blocks" needed to maintain cell division. When solid tumors are exposed to low pH, low oxygen and tumor microenvironment with nutrient deficiencies, the hypoxia-inducible factor-1 can be activated, which mediates the remodeling of metabolic patterns in tumor cells, namely, energy is obtained by circulating intracellular components (removing substrates such as proteins and lipid) or by utilizing adaptive metabolic reprogramming (such as glycolysis, autophagy and lipid metabolism, etc.). As a treatment scheme based on local heating of tumors, hyperthermia has a variety of anticancer mechanisms and can be used in combination with radiotherapy, chemotherapy and biological immune therapy. In this review, we briefly discussed the metabolic remodeling model mediated by hypoxia-inducible factor 1 in a hypoxia microenvironment, described the possible regulatory mechanism of hyperthermia on hypoxia-inducible factor-1 and prospected the application of hyperthermia in oral and maxillofacial tumors.

Objective:The investigate the roles and significance of HIF-1α and CYPJ in tongue squamous cell carcinoma cell (TSCC), and further evaluate the regulatory effect of hyperthermia (HT) on HIF-1α and CYPJ in TSCC cells.Methods:Eighty samples of cancer tissues and adjacent normal tissues from TSCC patients were collected. The expression levels of HIF-1α and CYPJ were detected by immunohistochemistry, Western blotting (WB) and fluorescence quantitative PCR, and the relationship between the expression levels of HIF-1α and CYPJ and clinicopathological characteristics was further analyzed. The expression levels of HIF-1α and CYPJ in Cal-27 cells under normoxic and hypoxic conditions for 24 h when combined with HT (42℃), chemotherapy and both were detected by qPCR and WB. Cell migration was detected by cell scratch test and cell apoptosis was measured by flow cytometry.Results:The expression levels of HIF-1α and CYPJ proteins in the tumor tissues of TSCC patients were higher than those in the adjacent normal tissues, which were significantly correlated with tumor size, TNM stage, differentiation degree and lymph node metastasis in TSCC patients (all P<0.05), whereas they were not correlated with gender or age (all P>0.05). The expression levels of HIF-1α and CYPJ in Cal-27 cells were significantly up-regulated in the hypoxic microenvironment (both P<0.05), which were also significantly enhanced by hyperthermia alone (both P<0.05). Compared with hyperthermia or chemotherapy alone, hyperthermia combined with chemotherapy significantly inhibited the expression of HIF-1α and CYPJ, suppressed cell migration and promoted cell apoptosis (all P<0.05). Conclusions:HIF-1α and CYPJ may be potential biomarkers for TSCC tumorigenicity and prognosis. In addition, tumor recurrence after hyperthermia may be due to the role of hyperthermia in triggering HIF-1α expression, which promotes the growth and survival of tumor cells adaptive to hyperthermia treatment by activating the downstream target genes, while hyperthermia combined with chemotherapy may be a promising treatment for TSCC.

With the in-depth study of tumor hyperthermia and tumor immune microenvironment (TIME), the role of hyperthermia in TIME has captivated increasing attention from scholars in recent years. Based upon recent research progress at home and abroad, the effect and mechanism of hyperthermia on several major immune cells and immune-related cytokines in the TIME were reviewed in this article. Comprehensive and deep understanding of the regulation of hyperthermia on the TIME could provide new ideas and methods for tumor treatment.