This Research Topic is one volume within the series "The Future of Checkpoint Immunotherapy: New Roads Ahead". Please see the series
here.
The field of cancer immunotherapy has witnessed a transformative shift with the advent of immune checkpoint inhibitors (ICIs), which have significantly altered the landscape of cancer treatment. These therapies, targeting CTLA4, PD1, and PDL1, have been approved for a wide array of cancer types, offering new hope for patients. However, a significant challenge remains: the development of primary or secondary resistance to ICIs in the majority of patients. This resistance poses a critical barrier to the efficacy of these treatments, necessitating a deeper understanding of the underlying mechanisms. Recent studies have begun to unravel the complex genetic, epigenetic, and microenvironmental factors contributing to resistance, yet many questions remain unanswered. Current research is focused on identifying these resistance pathways and developing strategies to counteract them, but a comprehensive understanding is still lacking. There is a pressing need for further investigation to enhance the therapeutic potential of ICIs and extend their benefits to a broader patient population.
This research topic aims to explore the diverse mechanisms underlying resistance to immune checkpoint inhibitors and to identify innovative strategies to overcome these challenges. By compiling cutting-edge clinical and translational research, as well as comprehensive reviews, we seek to elucidate the multifaceted nature of resistance. The goal is to foster collaboration and innovation, ultimately improving the efficacy and applicability of ICI therapies in cancer treatment. Key questions include understanding the genetic and epigenetic alterations that confer resistance, the role of the tumor microenvironment, and the impact of external factors such as the microbiome and exposome.
To gather further insights into the mechanisms and strategies to overcome resistance to ICIs, we welcome original clinical and translational research articles, as well as comprehensive review articles addressing, but not limited to, the following themes:
- Genetic and Epigenetic Mechanisms: Investigations into tumor genetic mutations, epigenetic modifications, and gene expression profiles associated with ICI resistance.
- Dysfunctional T-Cells: Mechanisms of T-cell exhaustion, the role of regulatory T-cells, and strategies to rejuvenate T-cell function.
- Tumor Microenvironment and Inflammation: Influence of the tumor microenvironment, interaction with immune cells, and modulation strategies.
- Role of Myeloid Cells: Contribution of MDSCs and TAMs, recruitment mechanisms, and therapeutic targeting.
- Cancer Cell Metabolism: Metabolic reprogramming, interaction with immune cells, and metabolic interventions.
- Exposome and Environmental Factors: Impact of environmental exposures, lifestyle factors, and integration of exposomic data.
- Microbiome: Role of the gut and tumor microbiome, microbiome-immune interactions, and therapeutic manipulation.
Topic Editor Stefano Cavalieri received financial support from AccMed, MultiMed Engineers srl, and Care Insight sas. The other Topic Editors declare no competing interests with regard to the Research Topic subject.