Heme metabolism: a metabolic interface in tumor radioimmunotherapy
10.13491/j.issn.1004-714X.2026.03.024
- VernacularTitle:血红素代谢——肿瘤放射免疫治疗的代谢交汇点
- Author:
Xun WANG
1
;
Yifan HAN
1
;
Zhiwu WANG
2
;
Zhenjiang LI
3
Author Information
1. School of Clinical Medicine, North China University of Science and Technology, Tangshan 063210, China;Department of Radiation Physics and Technology, Cancer Hospital of Shandong First Medical University, Jinan 250117, China;Department of Radiotherapy and Chemotherapy II, Tangshan People's Hospital, Tangshan 063001, China.
2. Department of Radiotherapy and Chemotherapy II, Tangshan People's Hospital, Tangshan 063001, China.
3. Department of Radiation Physics and Technology, Cancer Hospital of Shandong First Medical University, Jinan 250117, China.
- Publication Type:ReviewArticles
- Keywords:
Heme metabolism;
Tumor immune microenvironment;
Radioimmunotherapy;
Biomarkers;
Metabolic reprogramming
- From:
Chinese Journal of Radiological Health
2026;35(3):460-466
- CountryChina
- Language:Chinese
-
Abstract:
The combination of radiotherapy and immunotherapy is not merely a superposition of therapeutic effects but rather a dynamic competition involving radiation-induced damage, tissue repair programs, and antitumor immune amplification. Accumulating evidence indicates that heme metabolism does more than supply prosthetic groups. It acts as a critical interface connecting radiation stress, mitochondrial homeostasis, redox imbalance, iron metabolism, and tumor immune remodeling. Focusing on the "radiation-heme-immunotherapy" axis, this review systematically examines how radiation reshapes the heme synthesis-degradation network via reactive oxygen species (ROS) bursts, Nrf2/BACH1 responses, mitochondrial damage, and disruption of iron homeostasis. In turn, these changes reprogram the cGAS-STING-type I interferon axis, myeloid cell polarization, T-cell function, and the hypoxic/stromal state of the tumor microenvironment. We pay special attention to the functional paradox of heme oxygenase-1 (HO-1): it protects normal tissues from radiation injury yet promotes tumor tolerance. We propose that HO-1 outcomes are not determined solely by its expression level but are collectively shaped by the expressing cell type, the intensity and duration of induction, subcellular localization, and the microenvironmental context. Accordingly, HMOX1/HO-1 and related heme metabolic features may serve as novel biomarkers for patient stratification and sensitization of radioimmunotherapy combinations. The key to its clinical translation lies in establishing detection systems with spatial and temporal resolution and developing localized, temporally sequenced, and population-selective targeted therapeutic strategies.
