Biomedicines

Journal Browser

► Journal Browser

Special Issue Editor

Dr. Milica Perišić Nanut

E-Mail Website
Guest Editor

Department of Biotechnology, Jožef Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia
Interests: immune response in cancer; molecular mechanisms of immunosuppression; cysteine proteases and their inhibitors

Special Issue Information

Dear Colleague,

Peptidases control key functions of innate and adaptive immune responses. These include antigen processing and presentation of immunogenic peptides, cell cytotoxicity through activation of pro granzymes, cell adhesion and migration, chemokine activation and, thereby, leukocyte recruitment and response to various bacterial and viral infections. The expression of peptidases, their activity, and subcellular localization are associated with the distinct development and differentiation stages of immune cells. In contrast to the traditional view, recent studies have implicated peptidases in processes occurring outside lysosomes and endosomes. Peptidases can be found in the nucleus, the cytosol, and extracellularly, either secreted or bound to the plasma membrane. Peptidases localized outside lysosomes have been associated with different physiological processes such as prohormone activation, apoptosis and cell migration, while their extracellular localization is associated with degradation of the proteins of the extracellular matrix as part of tissue remodeling and cell migration. Dysregulation of their function has been associated with numerous pathological processes.

This Special Issue will comprise a selection of research papers and reviews that will provide current knowledge of the role of lysosomal and extralysosomal peptidases in immune cell function. New approaches using peptidases as potential therapeutic targets for improving immune cell function will be highlighted.

Dr. Milica Perišić Nanut
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

peptidase
peptidase inhibitor
effector function
immune response
signal transduction

Published Papers (2 papers)

Download All Papers

Research

Jump to: Review

13 pages, 1029 KiB

Open AccessArticle

Biomarkers for Outcome in Metastatic Melanoma in First Line Treatment with Immune Checkpoint Inhibitors

by Tanja Mesti, Cvetka Grašič Kuhar and Janja Ocvirk

Biomedicines 2023, 11(3), 749; https://doi.org/10.3390/biomedicines11030749 - 01 Mar 2023

Cited by 5 | Viewed by 1542

Abstract

Introduction: A high proportion of metastatic melanoma patients do not respond to immune checkpoint inhibitors (ICI), and until now, no validated biomarkers for response and survival have been known. Methods: We performed a retrospective analysis of outcomes in patients with metastatic melanoma treated with first-line ICI at the Institute of Oncology Ljubljana from January 2018 to December 2020. The immune-related adverse events (irAEs) and serum immune-inflammation parameters (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (LR), systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV)) were analyzed as potential biomarkers for response and survival. Survival rates were calculated using the Kaplan–Meier method and then compared with the log-rank test. Multivariate regression Cox analysis was used to determine independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Results: Median follow-up was 22.5 months. The estimated median progression-free survival (PFS) was 15 months (95% CI 3.3–26.2). The two-year survival rate (OS) was 66.6%. Among 129 treated patients, 24 (18.6%) achieved complete response, 28 (21.7%) achieved partial response, 26 (20.2%) had stable disease and 51 (39.5%) patients experienced a progressive disease. There was a higher response rate in patients with irAEs (p < 0.001) and high NLR before the second cycle of ICI (p = 0.052). Independent prognostic factors for PFS were irAE (HR 0.41 (95% CI 0.23–0.71)), SII before the first cycle of ICI (HR 1.94 (95% CI 1.09–3.45)) and PLR before the second cycle of ICI (HR 1.71 (95% CI 1.03–2.83)). The only independent prognostic factor for OS was SII before the first cycle of ICI (HR 2.60 (95% CI 0.91–7.50)). Conclusions: Patients with high pre-treatment levels of SII had a higher risk of progression and death; however, patients with irAEs in the high-SII group might respond well to ICI. Patients who develop irAEs and have high NLRs before the second ICI application have higher rates of CR and PR, which implicates their use as early biomarkers for responsiveness to ICI. Full article

(This article belongs to the Special Issue Role of Peptides and Peptidases in Immune Responses)

► Show Figures

Figure 1

Review

Jump to: Research

17 pages, 2047 KiB

Open AccessReview

Cysteine Cathepsins as Therapeutic Targets in Immune Regulation and Immune Disorders

by Emanuela Senjor, Janko Kos and Milica Perišić Nanut

Biomedicines 2023, 11(2), 476; https://doi.org/10.3390/biomedicines11020476 - 07 Feb 2023

Cited by 9 | Viewed by 2242

Abstract

Cysteine cathepsins, as the most abundant proteases found in the lysosomes, play a vital role in several processes—such as protein degradation, changes in cell signaling, cell morphology, migration and proliferation, and energy metabolism. In addition to their lysosomal function, they are also secreted and may remain functional in the extracellular space. Upregulation of cathepsin expression is associated with several pathological conditions including cancer, neurodegeneration, and immune-system dysregulation. In this review, we present an overview of cysteine-cathepsin involvement and possible targeting options for mitigation of aberrant function in immune disorders such as inflammation, autoimmune diseases, and immune response in cancer. Full article

(This article belongs to the Special Issue Role of Peptides and Peptidases in Immune Responses)

► Show Figures