About this Research Topic
The progressive understanding of the anti-tumor capabilities of the immune system has ignited considerable enthusiasm within the oncology community over the past decade. Immune checkpoint inhibitors (ICIs) have emerged as a paradigm shift of a new era in cancer treatment. To date, the FDA and EMA have approved 11 different versions of antibodies targeting CTLA4, PD1, and PDL1 for more than 65 different indications across more than 20 cancer types, either as monotherapies or as a combination therapy.
Despite the success of ICIs, the majority of patients develop primary or secondary resistance to these therapies. Understanding and overcoming resistance mechanisms is critical for enhancing therapeutic outcomes and expanding the benefits of ICIs to a larger cohort of patients.
This Research Topic invites original clinical and translational research articles, as well as comprehensive review articles, focusing on the diverse mechanisms underlying resistance to ICIs. We aim to compile a collection of cutting-edge studies that elucidate the multifaceted nature of resistance, offering insights into potential strategies for overcoming these barriers.
Submissions may address, but are not limited to, the following aspects of resistance to ICIs:
Genetic and Epigenetic Mechanisms:
• Investigations into tumor genetic mutations and alterations that confer resistance to ICIs.
• Epigenetic modifications and their role in modulating immune response to ICIs.
• Studies on gene expression profiles associated with ICI resistance.
Dysfunctional T-Cells:
• Mechanisms of T-cell exhaustion and dysfunction in the context of ICI therapy.
• Role of regulatory T-cells and their impact on therapeutic resistance.
• Strategies to rejuvenate T-cell function and enhance responsiveness to ICIs.
Tumor Microenvironment and Inflammation:
• Influence of the inflammatory status of the tumor microenvironment on ICI efficacy.
• Interaction between tumor cells and the immune microenvironment contributing to resistance.
• Modulation of the tumor microenvironment to overcome resistance.
Role of Myeloid Cells:
• Contribution of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) to ICI resistance.
• Mechanistic insights into the recruitment and function of myeloid cells in resistant tumors.
• Therapeutic targeting of myeloid cells to enhance ICI efficacy.
Cancer Cell Metabolism:
• Metabolic reprogramming of cancer cells as a mechanism of resistance to ICIs.
• Interaction between cancer cell metabolism and immune cell function.
• Metabolic interventions to potentiate ICI responses.
Exposome and Environmental Factors:
• Impact of environmental exposures on the effectiveness of ICIs.
• Studies on lifestyle factors, diet, and pollutants influencing ICI resistance.
• Integration of exposomic data in predicting and managing resistance.
Microbiome:
• Role of the gut and tumor microbiome in modulating responses to ICIs.
• Mechanistic insights into microbiome-immune interactions affecting ICI resistance.
• Therapeutic manipulation of the microbiome to overcome resistance.
By compiling a comprehensive collection of studies on resistance to ICIs, this Research Topic aims to advance our understanding of the underlying mechanisms and identify novel strategies to overcome these barriers. We hope to foster collaboration and innovation in the field, ultimately improving the efficacy and applicability of ICI therapies in cancer treatment.
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.
Keywords: exposome, ICI resistance, immune biomarkers, immune checkpoint inhibitors, immune metabolism, immune microenvironment, immune resistance, microbiome, T cells
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.