The burgeoning field of immunotherapy has illuminated the path toward combating various cancers by harnessing the body's immune response. Central to this discourse is the phenomenon of immune cell exhaustion, a state where prolonged exposure to cancer antigens and the suppressive tumor microenvironment (TME) significantly impairs the efficacy of immune cells. Particularly, T cells, pivotal in the anti-tumor immune response, alongside NK cells, B cells, and macrophages, exhibit marked declines in their functional capacities. This exhaustion is not merely a depletion of cell populations, but a complex, multifaceted state characterized by altered expression of inhibitory receptors (e.g., PD-1, CTLA-4), metabolic dysregulation, and transcriptional changes leading to diminished cytokine production and proliferative capacity. The tumor microenvironment plays a crucial role in this process, employing mechanisms such as upregulation of immune checkpoint ligands, secretion of immunosuppressive cytokines (e.g., TGF-ß, IL-10), and recruitment of regulatory immune cells (e.g., Tregs, MDSCs), thereby creating an immunosuppressive milieu that fosters tumor growth and metastasis. Understanding the intricate interactions and pathways leading to immune cell exhaustion within the TME is critical for developing next-generation immunotherapies.
The goal of this Research Topic is to investigate the mechanisms and consequences of immune cell exhaustion in cancer therapy, focusing on the tumor microenvironment's role. It aims to explore the functions of specific immune cells, signaling pathways, and transcriptional and metabolic shifts that lead to exhaustion. This initiative seeks to uncover new therapeutic targets and strategies to revitalize exhausted immune cells, thus improving immunotherapy outcomes and providing new hope for cancer patients. Through this, we aspire to bridge basic science with therapeutic advances, facilitating breakthroughs in tackling immune cell exhaustion. We welcome submissions that include but are not limited to the following topics:
1) Cellular and molecular mechanisms of immune cell exhaustion.
2) Exhaustion phenomena in various immune cells (NK cells, B cells, macrophages, etc.) in cancer.
3) Complex networks of immune cell interactions within the tumor microenvironment.
4) Investigating immune cell heterogeneity and states of exhaustion using single-cell sequencing technology.
5) Mapping the spatial distribution of immune cells within the tumor microenvironment using spatial transcriptomics.
6) Novel strategies and therapeutic interventions to reverse exhausted immune cell function.
7) The role and challenges of bioinformatics in elucidating immune cell exhaustion.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
The burgeoning field of immunotherapy has illuminated the path toward combating various cancers by harnessing the body's immune response. Central to this discourse is the phenomenon of immune cell exhaustion, a state where prolonged exposure to cancer antigens and the suppressive tumor microenvironment (TME) significantly impairs the efficacy of immune cells. Particularly, T cells, pivotal in the anti-tumor immune response, alongside NK cells, B cells, and macrophages, exhibit marked declines in their functional capacities. This exhaustion is not merely a depletion of cell populations, but a complex, multifaceted state characterized by altered expression of inhibitory receptors (e.g., PD-1, CTLA-4), metabolic dysregulation, and transcriptional changes leading to diminished cytokine production and proliferative capacity. The tumor microenvironment plays a crucial role in this process, employing mechanisms such as upregulation of immune checkpoint ligands, secretion of immunosuppressive cytokines (e.g., TGF-ß, IL-10), and recruitment of regulatory immune cells (e.g., Tregs, MDSCs), thereby creating an immunosuppressive milieu that fosters tumor growth and metastasis. Understanding the intricate interactions and pathways leading to immune cell exhaustion within the TME is critical for developing next-generation immunotherapies.
The goal of this Research Topic is to investigate the mechanisms and consequences of immune cell exhaustion in cancer therapy, focusing on the tumor microenvironment's role. It aims to explore the functions of specific immune cells, signaling pathways, and transcriptional and metabolic shifts that lead to exhaustion. This initiative seeks to uncover new therapeutic targets and strategies to revitalize exhausted immune cells, thus improving immunotherapy outcomes and providing new hope for cancer patients. Through this, we aspire to bridge basic science with therapeutic advances, facilitating breakthroughs in tackling immune cell exhaustion. We welcome submissions that include but are not limited to the following topics:
1) Cellular and molecular mechanisms of immune cell exhaustion.
2) Exhaustion phenomena in various immune cells (NK cells, B cells, macrophages, etc.) in cancer.
3) Complex networks of immune cell interactions within the tumor microenvironment.
4) Investigating immune cell heterogeneity and states of exhaustion using single-cell sequencing technology.
5) Mapping the spatial distribution of immune cells within the tumor microenvironment using spatial transcriptomics.
6) Novel strategies and therapeutic interventions to reverse exhausted immune cell function.
7) The role and challenges of bioinformatics in elucidating immune cell exhaustion.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.