In the tumor microenvironment (TME), T lymphocyte failure occurs under conditions of sustained antigenic stimulation combined with hypoxia and nutritional stress. T cell failure is characterized by a progressive loss of proliferative capacity, the emergence of cytotoxic effector functions, and upregulation of co-inhibitory molecular functions, accompanied by intense epigenetic remodeling and metabolic reprogramming processes. In addition to ATP production, mitochondrial depletion is a highly dynamic signaling organelle that indicates the fate and function of immune cells. Indeed, dramatic mitochondrial remodeling, including morphological and kinetic alterations, occurs during T cell activation, effector, and memory differentiation. Although proper reactive oxygen species (ROS) production is essential for antigen-activated T cells to acquire effector functions, tumor-infiltrating T lymphocytes (TILs) frequently exhibit mitochondrial damage or fragmentation, accompanied by abnormal mitochondrial ROS (mtROS) production and impaired oxidative phosphorylation (OXPHOS). T cell receptor (TCR) recognition of antigen T cell receptor (TCR) recognition is critical for T cell activation and effector functions. However, it is currently not clear to researchers that disruption of mitochondrial integrity or activity within T cells would indicate that the cells enter a terminal state of failure.
Nowadays, scientists are aware that chronic hypoxia exposure induces oxidative stress and mitochondrial autophagy in tumor cells. However, researchers still need further studies to elucidate how chronic stimuli and tumor cell-derived factors drive abnormal mitochondrial function in T cells. In addition, researchers need to delve into how alterations in mitochondrial metabolism regulate epigenetic programs (histone modifications and DNA methylation modifications) that drive the exhaustion of TILs. A deeper understanding of the molecular mechanisms behind this may help scientists manipulate TCR-T and CAR-T cells through epigenetic engineering approaches to achieve superior organismal anti-tumor effects.
Defective mitochondrial autophagy or impaired oxidative phosphorylation processes may induce the production of reactive oxygen species in mitochondria, which promotes the depletion program of T cells and can limit the proliferation and self-renewal of T cells. In this study topic, we anticipate that our research topic will help expand the research community's understanding of the latest and rapidly evolving areas of TME, mitochondrial damage, and immunity for further thorough investigations that will certainly facilitate the management of multiple fatal diseases.
We welcome the submission of Original Research and Review articles. Subtopics of interest include, but are not limited to:
1) The association between mitochondrial damage and T cell exhaustion in the tumor microenvironment;
2) Epigenetic remodeling and metabolic reprogramming process of immune cells;
3) The impact of exhaustion of immune cells on immunotherapy.
In the tumor microenvironment (TME), T lymphocyte failure occurs under conditions of sustained antigenic stimulation combined with hypoxia and nutritional stress. T cell failure is characterized by a progressive loss of proliferative capacity, the emergence of cytotoxic effector functions, and upregulation of co-inhibitory molecular functions, accompanied by intense epigenetic remodeling and metabolic reprogramming processes. In addition to ATP production, mitochondrial depletion is a highly dynamic signaling organelle that indicates the fate and function of immune cells. Indeed, dramatic mitochondrial remodeling, including morphological and kinetic alterations, occurs during T cell activation, effector, and memory differentiation. Although proper reactive oxygen species (ROS) production is essential for antigen-activated T cells to acquire effector functions, tumor-infiltrating T lymphocytes (TILs) frequently exhibit mitochondrial damage or fragmentation, accompanied by abnormal mitochondrial ROS (mtROS) production and impaired oxidative phosphorylation (OXPHOS). T cell receptor (TCR) recognition of antigen T cell receptor (TCR) recognition is critical for T cell activation and effector functions. However, it is currently not clear to researchers that disruption of mitochondrial integrity or activity within T cells would indicate that the cells enter a terminal state of failure.
Nowadays, scientists are aware that chronic hypoxia exposure induces oxidative stress and mitochondrial autophagy in tumor cells. However, researchers still need further studies to elucidate how chronic stimuli and tumor cell-derived factors drive abnormal mitochondrial function in T cells. In addition, researchers need to delve into how alterations in mitochondrial metabolism regulate epigenetic programs (histone modifications and DNA methylation modifications) that drive the exhaustion of TILs. A deeper understanding of the molecular mechanisms behind this may help scientists manipulate TCR-T and CAR-T cells through epigenetic engineering approaches to achieve superior organismal anti-tumor effects.
Defective mitochondrial autophagy or impaired oxidative phosphorylation processes may induce the production of reactive oxygen species in mitochondria, which promotes the depletion program of T cells and can limit the proliferation and self-renewal of T cells. In this study topic, we anticipate that our research topic will help expand the research community's understanding of the latest and rapidly evolving areas of TME, mitochondrial damage, and immunity for further thorough investigations that will certainly facilitate the management of multiple fatal diseases.
We welcome the submission of Original Research and Review articles. Subtopics of interest include, but are not limited to:
1) The association between mitochondrial damage and T cell exhaustion in the tumor microenvironment;
2) Epigenetic remodeling and metabolic reprogramming process of immune cells;
3) The impact of exhaustion of immune cells on immunotherapy.