Protease Inhibition in Immune Response and Cancer Biology

Proteases are pivotal in regulating immune homeostasis and tumour biology. Their activity coordinates processes from antigen processing and cytokine activation in innate and adaptive immunity to degradation of the extracellular matrix during tumour invasion and metastasis. Endogenous protease inhibitors calibrate this proteolytic balance, preventing excessive tissue damage and modulating inflammatory cascades. Dysregulated protease–inhibitor networks underlie chronic inflammation, autoimmune disorders and cancer progression. In the immune context, serine protease inhibitors limit neutrophil elastase and granzyme activity to resolve inflammation, while in cancer, altered expression of inhibitors such as secretory leukocyte protease inhibitor can either suppress tumour cell invasion by blocking matrix metalloproteinases or paradoxically promote metastasis through non‐canonical signalling. Therapeutic targeting of protease inhibition holds promise for controlling inflammatory diseases and limiting tumour dissemination.

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Protease Inhibition in Immune Response and Cancer Biology publication trend

The graph below shows the total number of articles in protease inhibition in immune response and cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Protease: Enzyme that catalyses the hydrolysis of peptide bonds in proteins.

Protease inhibitor: Molecule that binds to proteases and prevents substrate cleavage.

Serine protease: Class of proteases that utilise a serine residue at the active site.

Matrix metalloproteinase (MMP): Zinc-dependent endopeptidase involved in extracellular matrix remodelling.

Secretory leukocyte protease inhibitor (SLPI): Endogenous antiprotease with anti-inflammatory and immunomodulatory functions.

Nuclear factor-κB (NF-κB): Transcription factor that regulates genes involved in inflammation, immunity and cell survival.

References

1. Secretory Leukocyte Protease Inhibitor (SLPI) in mucosal tissues: Protects against inflammation, but promotes cancer. Cytokine & Growth Factor Reviews (2021).
2. Secretory leukocyte protease inhibitor (SLPI) as a potential target for inhibiting metastasis of triple-negative breast cancers. Oncotarget (2017).
3. Neutrophils and Activated Macrophages Control Mucosal Immunity by Proteolytic Cleavage of Antileukoproteinase. Frontiers in Immunology (2018).
4. Secretory Leucoprotease Inhibitor Prevents Lipopolysaccharide-induced IκBα Degradation without Affecting Phosphorylation or Ubiquitination*. Journal of Biological Chemistry (2002).