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Front. Immunol. | doi: 10.3389/fimmu.2019.02037

Cysteine cathepsins in tumor-associated immune cells

  • 1Faculty of Pharmacy, University of Ljubljana, Slovenia
  • 2UCLA School of Dentistry, United States

Cysteine cathepsins are key regulators of the innate and adaptive arms of the immune system. Their expression, activity and subcellular localization are associated with the distinct development and differentiation stages of immune cells. They promote the activation of innate myeloid immune cells since they contribute to toll-like receptor signaling and to cytokine secretion. Furthermore, they control lysosomal biogenesis and autophagic flux, thus affecting innate immune cell survival and polarization. They also regulate bidirectional communication between the cell exterior and the cytoskeleton, thus influencing cell interactions, morphology and motility. Importantly, cysteine cathepsins contribute to the priming of adaptive immune cells by controlling antigen presentation and are involved in cytotoxic granule mediated killing in cytotoxic T lymphocytes and natural killer cells. Dysregulated proteolysis also contributes significantly to tumor progression by modulation of the antitumor immune response. Tumor-associated myeloid cells, such as tumor-associated macrophages and myeloid-derived suppressor cells, are known for their tumor promoting and immunosuppressive functions, and constitute the major source of cysteine cathepsin activity in cancer.

Keywords: Cathepsins, Cystatin, Immune responce, tumor associated macrophage, myeloid derived suppresser cells

Received: 31 May 2019; Accepted: 12 Aug 2019.

Edited by:

Khashayarsha Khazaie, Mayo Clinic College of Medicine & Science, United States

Reviewed by:

Julian Pardo, Fundacion Agencia Aragonesa para la Investigacion y el Desarrollo, Spain
Elias Gounaris, Feinberg School of Medicine, Northwestern University, United States
Milica M. Perisic Nanut, Jožef Stefan Institute (IJS), Slovenia  

Copyright: © 2019 Jakoš, Pišlar, Jewett and Kos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Janko Kos, University of Ljubljana, Faculty of Pharmacy, Ljubljana, 1000, Slovenia, janko.kos@ffa.uni-lj.si