Beyond Checkpoints––the HLA System and other New Targets

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (10 September 2022) | Viewed by 5274

Special Issue Editor


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INTELLEXON GmbH, Keltenstrasse 27, 82343 Pöcking, Germany
Interests: implantation failure; pregnancy loss; pregnancy disorders; microbiome; immuno-oncology; HLA system in cancer
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Special Issue Information

Dear Colleagues,

In the wake of the Nobel Prizes concerning checkpoint/checkpoint inhibitor therapy, it is now evident that immuno-oncology is of growing importance in the scientific community. However, although the therapy options of checkpoints, their inhibitors (or even activators), and their ligands have proved to be useful, they only represent a very minor part of immunological tumor control and therefore of possible therapeutic applications.

The dominating cellular identification and communication system in humans is the HLA (Human Leukocyte Antigen) system, which represents class I and class II of the Major Histocompatibility Complex (MHC) and also partially extends to class III. This dominant system is therefore worthy of investigation with respect to the regulation of implantation/pregnancy and, in particular, to the immunoregulation of carcinogenesis.

Certain groups in the HLA system, especially the nonclassical group HLA-G (class Ib) with its seven isoforms, are well documented in their crucial role in the overriding the immune system with malignant tumors. However, there are also other aspects and other nonclassical groups, e.g., HLA-F and its isoforms, whose role in the manipulation of the immune system through malignant tumors remains to be elucidated.

Owing to the above, a more in-depth investigation into the HLA system has become more than necessary. However, there are also other new targets “in the pipeline” that should not be neglected, e.g., growth factors, their receptors, and tumor-bound expression/overexpression.

Therefore, we believe that it of great significance to collate the “state of the art” concerning the HLA system, new targets beyond checkpoints, and their significance, particularly in oncology, which has led to the original studies and overviews presented in this Special Issue. In addition, the issue also aims to trace the direction of current scientific studies and their potential importance for diagnosis and therapy in the future.

Prof. Dr. Wolfgang Würfel
Guest Editor

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Keywords

  • HLA
  • oncology
  • immunoregulation
  • cancer
  • reproduction

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Published Papers (2 papers)

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Research

12 pages, 1950 KiB  
Article
Immunopeptidome Diversity in Chronic Lymphocytic Leukemia Identifies Patients with Favorable Disease Outcome
by Maddalena Marconato, Yacine Maringer, Juliane S. Walz, Annika Nelde and Jonas S. Heitmann
Cancers 2022, 14(19), 4659; https://doi.org/10.3390/cancers14194659 - 25 Sep 2022
Cited by 2 | Viewed by 1659
Abstract
Chronic lymphocytic leukemia (CLL) is characterized by recurrent relapses and resistance to treatment, even with novel therapeutic approaches. Despite being considered as a disease with low mutational burden and thus poor immunogenic, CLL seems to retain the ability of eliciting specific T cell [...] Read more.
Chronic lymphocytic leukemia (CLL) is characterized by recurrent relapses and resistance to treatment, even with novel therapeutic approaches. Despite being considered as a disease with low mutational burden and thus poor immunogenic, CLL seems to retain the ability of eliciting specific T cell activation. Accordingly, we recently found non-mutated tumor-associated antigens to play a central role in CLL immunosurveillance. Here, we investigated the association of total and CLL-exclusive HLA class I and HLA class II peptide presentation in the mass spectrometry-defined immunopeptidome of leukemic cells with clinical features and disease outcome of 57 CLL patients. Patients whose CLL cells present a more diverse immunopeptidome experienced fewer relapses. During the follow-up phase of up to 10 years, patients with an HLA class I-restricted presentation of high numbers of total and CLL-exclusive peptides on their malignant cells showed a more favorable disease course with a prolonged progression-free survival (PFS). Overall, our results suggest the existence of an efficient T cell-based immunosurveillance mediated by CLL-associated tumor antigens, supporting ongoing efforts in developing T cell-based immunotherapeutic strategies for CLL. Full article
(This article belongs to the Special Issue

Beyond Checkpoints––the HLA System and other New Targets

)
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13 pages, 1915 KiB  
Article
HLA-DR Presentation of the Tumor Antigen MSLN Associates with Clinical Outcome of Ovarian Cancer Patients
by Christian M. Tegeler, Jonas Scheid, Hans-Georg Rammensee, Helmut R. Salih, Juliane S. Walz, Jonas S. Heitmann and Annika Nelde
Cancers 2022, 14(9), 2260; https://doi.org/10.3390/cancers14092260 - 30 Apr 2022
Cited by 5 | Viewed by 2884
Abstract
T-cell recognition of HLA-presented antigens is central for the immunological surveillance of malignant disease and key for the development of novel T-cell-based immunotherapy approaches. In recent years, large-scale immunopeptidome studies identified naturally presented tumor-associated antigens for several malignancies. Regarding ovarian carcinoma (OvCa), Mucin-16 [...] Read more.
T-cell recognition of HLA-presented antigens is central for the immunological surveillance of malignant disease and key for the development of novel T-cell-based immunotherapy approaches. In recent years, large-scale immunopeptidome studies identified naturally presented tumor-associated antigens for several malignancies. Regarding ovarian carcinoma (OvCa), Mucin-16 (MUC16) and Mesothelin (MSLN) were recently described as the top HLA class I- and HLA class II-presented tumor antigens, respectively. Here, we investigate the role and impact of immunopeptidome-presented tumor antigens on the clinical outcomes of 39 OvCa patients with a follow-up time of up to 50 months after surgery. Patients with a HLA-restricted presentation of high numbers of different MSLN-derived peptides on their tumors exhibited significantly prolonged progression-free (PFS) and overall survival (OS), whereas the presentation of MUC16-derived HLA class I-restricted peptides had no impact. Furthermore, a high HLA-DRB gene expression was associated with increased PFS and OS. In line, in silico prediction revealed that MSLN-derived HLA class II-presented peptides are predominantly presented on HLA-DR allotypes. In conclusion, the correlation of MSLN tumor antigen presentation and HLA-DRB gene expression with prolonged survival indicates a central role of CD4+ T-cell responses for tumor immune surveillance in OvCa, and highlights the importance of immunopeptidome-guided tumor antigen discovery. Full article
(This article belongs to the Special Issue

Beyond Checkpoints––the HLA System and other New Targets

)
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