Cancer immunotherapy has achieved great success in the past few years. However, the exhaustion of T cells or NK cells can lead to the failure of tumor control and limit the complete response and overall efficacy of cancer immunotherapy against solid tumors. The exhausted T cells or NK cells in the tumor microenvironment exhibit imbalanced expression of inhibitory and activating receptors, downregulated expression of effector cytokines, and reduced cytotoxicity, and this process is modulated by multiple factors, such as cytokines, soluble mediators, metabolic reprogramming, epigenetic remodeling, or transcription factors. Increasing evidence suggests that the reinvigoration of exhausted T cells or NK cells represents an inspiring strategy for improved efficacy and significant breakthrough in cancer immunotherapy by diverse methods, such as a variety of cytokines, soluble mediators, or transcription factors. For example, a type II cytokine IL-10 reinvigorates terminally exhausted CD8+ T cells through metabolic reprogramming for dramatically enhanced cancer immunotherapy. Overexpression of the canonical AP-1 transcription factor c-Jun in CAR T cells induces robust exhaustion resistance. Soluble mediators like nicotinamide ribose or N-acetylcysteine could reverse chronic stimulation-driven T cell exhaustion by sustaining mitochondrial fitness. Hence, our present topic aims to adopt the above strategies to reverse or prevent T cell exhaustion or NK cell exhaustion through various mechanisms, including metabolic reprogramming, epigenetic remodeling, or transcriptional modulation of immune cells or/and tumor cells in the aspects of cancer immunotherapy.
The goal of this research topic is to provide a forum for advancing research on the contribution of cytokines, soluble mediators, or transcription factors to the modulation of T cell or NK cell exhaustion in cancer immunity and immunotherapy. It includes fundamental discoveries of new mechanisms of action about the exhaustion of immune cells or novel bioengineering applications of existing theories to reverse or prevent the exhaustion of immune cells for enhanced cancer immunotherapy. All overview and original papers, whether theoretical or experimental in nature, are welcome.
The present topic has the bullet points below, which are also the specific themes we would like contributors to address:
1) Mechanisms of T cell or NK cell exhaustion in the tumor microenvironment
2) Responses of exhausted T cells or NK cells to cytokines, soluble mediators, or transcription factors
3) Reversing or preventing T cell or NK cell exhaustion through metabolic reprogramming, epigenetic remodeling, or/and transcriptional modulation
4) Treatment of cytokines, soluble mediators, or transcription factors for enhanced cancer immunotherapy
5) Human clinical trials of exhaustion-resistant T cells or NK cell therapy against cancer
6) Combination studies – e.g. tumor growth inhibitors + reinvigoration of exhausted T cells or/and NK cells
7) Improving cancer immunotherapy by engineering cytokines, soluble mediators, or transcription factors
Cancer immunotherapy has achieved great success in the past few years. However, the exhaustion of T cells or NK cells can lead to the failure of tumor control and limit the complete response and overall efficacy of cancer immunotherapy against solid tumors. The exhausted T cells or NK cells in the tumor microenvironment exhibit imbalanced expression of inhibitory and activating receptors, downregulated expression of effector cytokines, and reduced cytotoxicity, and this process is modulated by multiple factors, such as cytokines, soluble mediators, metabolic reprogramming, epigenetic remodeling, or transcription factors. Increasing evidence suggests that the reinvigoration of exhausted T cells or NK cells represents an inspiring strategy for improved efficacy and significant breakthrough in cancer immunotherapy by diverse methods, such as a variety of cytokines, soluble mediators, or transcription factors. For example, a type II cytokine IL-10 reinvigorates terminally exhausted CD8+ T cells through metabolic reprogramming for dramatically enhanced cancer immunotherapy. Overexpression of the canonical AP-1 transcription factor c-Jun in CAR T cells induces robust exhaustion resistance. Soluble mediators like nicotinamide ribose or N-acetylcysteine could reverse chronic stimulation-driven T cell exhaustion by sustaining mitochondrial fitness. Hence, our present topic aims to adopt the above strategies to reverse or prevent T cell exhaustion or NK cell exhaustion through various mechanisms, including metabolic reprogramming, epigenetic remodeling, or transcriptional modulation of immune cells or/and tumor cells in the aspects of cancer immunotherapy.
The goal of this research topic is to provide a forum for advancing research on the contribution of cytokines, soluble mediators, or transcription factors to the modulation of T cell or NK cell exhaustion in cancer immunity and immunotherapy. It includes fundamental discoveries of new mechanisms of action about the exhaustion of immune cells or novel bioengineering applications of existing theories to reverse or prevent the exhaustion of immune cells for enhanced cancer immunotherapy. All overview and original papers, whether theoretical or experimental in nature, are welcome.
The present topic has the bullet points below, which are also the specific themes we would like contributors to address:
1) Mechanisms of T cell or NK cell exhaustion in the tumor microenvironment
2) Responses of exhausted T cells or NK cells to cytokines, soluble mediators, or transcription factors
3) Reversing or preventing T cell or NK cell exhaustion through metabolic reprogramming, epigenetic remodeling, or/and transcriptional modulation
4) Treatment of cytokines, soluble mediators, or transcription factors for enhanced cancer immunotherapy
5) Human clinical trials of exhaustion-resistant T cells or NK cell therapy against cancer
6) Combination studies – e.g. tumor growth inhibitors + reinvigoration of exhausted T cells or/and NK cells
7) Improving cancer immunotherapy by engineering cytokines, soluble mediators, or transcription factors
