Lysosomal peptidases have a fundamental role in maintaining physiological homeostasis. The most predominant peptidases in lysosomes of mammalian cells can be grouped into four major families: aspartic cathepsins (D and E), serine cathepsins (A and G), the single-member family of asparagine endopeptidase (AEP), which is a cysteine peptidase with a fold more related to the caspases than the C1-family of peptidases and finally cysteine cathepsins (B, C, F, H, K, L, O, S, V,W, and X/Z) annotated as clan CA, family C1a. Except a general function of lysosomal peptidases in protein turnover, they play important roles in several cellular important immunological processes such as: major histocompatibility complex class II (MHC II)-mediated antigen processing and presentation, Toll-like receptor signalling, cytokine activation and secretion, apoptosis, autophagy, immune cell differentiation, migration and cytotoxicity. Their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis.
In tumour cells, lysosomal peptidases are involved in numerous processes throughout malignant progression. Their translocation from the endosomal/lysosomal pathway to the nucleus, cytoplasm, plasma membrane and extracellular space enables the activation of a variety of cancer-promoting proteins. Lysosomal peptidases interfere with cytokine/chemokine signalling, regulate cell adhesion and migration and promote cell invasion, angiogenesis and metastasis. Furthermore, lysosomal peptidases modify growth factors and receptors involved in tyrosine kinase-dependent pathways such as MAPK, Akt and JNK, thus representing key signalling tools for the activation of tumour cell growth and proliferation. With these complex actions, lysosomal peptidases institute an important regulatory mechanism for fine-tuning the anti-tumour immune response.
The goal of this special issue is to explore the role of lysosomal peptidases in immune cell function and tumour immune evasion and to emphasize new approaches using lysosomal peptidases as potential therapeutic targets.
• Lysosomal peptidases in tumour immune evasion
• Lysosomal peptidases as new biomarkers
• New therapeutic targets for improvement of cancer immunotherapies
Lysosomal peptidases have a fundamental role in maintaining physiological homeostasis. The most predominant peptidases in lysosomes of mammalian cells can be grouped into four major families: aspartic cathepsins (D and E), serine cathepsins (A and G), the single-member family of asparagine endopeptidase (AEP), which is a cysteine peptidase with a fold more related to the caspases than the C1-family of peptidases and finally cysteine cathepsins (B, C, F, H, K, L, O, S, V,W, and X/Z) annotated as clan CA, family C1a. Except a general function of lysosomal peptidases in protein turnover, they play important roles in several cellular important immunological processes such as: major histocompatibility complex class II (MHC II)-mediated antigen processing and presentation, Toll-like receptor signalling, cytokine activation and secretion, apoptosis, autophagy, immune cell differentiation, migration and cytotoxicity. Their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis.
In tumour cells, lysosomal peptidases are involved in numerous processes throughout malignant progression. Their translocation from the endosomal/lysosomal pathway to the nucleus, cytoplasm, plasma membrane and extracellular space enables the activation of a variety of cancer-promoting proteins. Lysosomal peptidases interfere with cytokine/chemokine signalling, regulate cell adhesion and migration and promote cell invasion, angiogenesis and metastasis. Furthermore, lysosomal peptidases modify growth factors and receptors involved in tyrosine kinase-dependent pathways such as MAPK, Akt and JNK, thus representing key signalling tools for the activation of tumour cell growth and proliferation. With these complex actions, lysosomal peptidases institute an important regulatory mechanism for fine-tuning the anti-tumour immune response.
The goal of this special issue is to explore the role of lysosomal peptidases in immune cell function and tumour immune evasion and to emphasize new approaches using lysosomal peptidases as potential therapeutic targets.
• Lysosomal peptidases in tumour immune evasion
• Lysosomal peptidases as new biomarkers
• New therapeutic targets for improvement of cancer immunotherapies