Cysteine Peptidases in Antigen-Presenting Cells as a Promising Target for Improving Anti-Tumor Immunity

Antigen-presenting cells (APCs), such as dendritic cells and macrophages, are essential for initiating and regulation of anti-tumor T cell responses. Central to this function is antigen processing, where cysteine peptidases—notably cathepsins B, L, and S—play a critical role in two stages of this process: a) generation of peptides for MHC II presentation thus shaping the immunopeptidome, and b) degradation of invariant chain thus enabling MHC class II-peptide complex formation. Also, there are data regarding the role of cysteine peptidases in regulation of cross-presentation in dendritic cells, that is of particular importance for anti-tumor immune response mediated by cytotoxic CD8+ T cells.

In addition to the role in antigen presentation, cysteine peptidases modulate endosomal trafficking, Toll-like receptor (TLR) signaling (especially for intracellular TLR 3,7,8,9), and APC morphology, maturation and migration. Their dysregulated activity contributes to immune evasion and tumor-promoting inflammation, while selective inhibition can preserve antigenic epitopes, boost CD8⁺ T cell priming, and reprogram the tumor microenvironment toward immunostimulation.

This Research Topic aims to explore the immunological potential of this underexploited protease family by putting into spotlight novel strategies targeting cysteine peptidases to enhance APC function and anti-tumor immunity.

To gather further insights into enhancing anti-tumor responses via cysteine peptidases, we welcome articles (original research, reviews, and brief reports) addressing, but not limited to, the following themes:

• Mechanistic insights of cysteine peptidases in antigen presentation.

• Therapeutic modulation strategies for cysteine peptidases.

• Translational applications in enhancing checkpoint therapy and vaccine development.

• Impact of cysteine peptidases on TLR signaling and endosomal trafficking.

• Reprogramming of the tumor microenvironment through APC function enhancement.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: cysteine peptidases, antigen presenting cells, anti-tumor responses

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.