Journal Article (Review Article)

DKFZ-2022-02503

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Is HLA type a possible cancer risk modifier in Lynch syndrome?

Ahadova, A. (First author)DKFZ* ; Witt, J.DKFZ* ; Haupt, S. ; Gallon, R. ; Hüneburg, R. ; Nattermann, J. ; Ten Broeke, S. ; Bohaumilitzky, L.DKFZ* ; Hernandez-Sanchez, A.DKFZ* ; Santibanez-Koref, M. ; Jackson, M. S. ; Ahtiainen, M. ; Pylvänäinen, K. ; Andini, K. ; Grolmusz, V. K. ; Möslein, G. ; Dominguez-Valentin, M. ; Møller, P. ; Fürst, D. ; Sijmons, R. ; Borthwick, G. M. ; Burn, J. ; Mecklin, J.-P. ; Heuveline, V. ; von Knebel Doeberitz, M.DKFZ* ; Seppälä, T. ; Kloor, M. (Last author)DKFZ*

2023
Wiley-Liss Bognor Regis

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Please use a persistent id in citations: doi:10.1002/ijc.34312

Abstract: Lynch syndrome (LS) is the most common inherited cancer syndrome. It is inherited via a monoallelic germline variant in one of the DNA mismatch repair (MMR) genes. LS carriers have a broad 30% to 80% risk of developing various malignancies, and more precise, individual risk estimations would be of high clinical value, allowing tailored cancer prevention and surveillance. Due to MMR deficiency, LS cancers are characterized by the accumulation of frameshift mutations leading to highly immunogenic frameshift peptides (FSPs). Thus, immune surveillance is proposed to inhibit the outgrowth of MMR-deficient cell clones. Recent studies have shown that immunoediting during the evolution of MMR-deficient cancers leads to a counter-selection of highly immunogenic antigens. The immunogenicity of FSPs is dependent on the antigen presentation. One crucial factor determining antigen presentation is the HLA genotype. Hence, a LS carrier's HLA genotype plays an important role in the presentation of FSP antigens to the immune system, and may influence the likelihood of progression from precancerous lesions to cancer. To address the challenge of clarifying this possibility including diverse populations with different HLA types, we have established the INDICATE initiative (Individual cancer risk by HLA type, http://indicate-lynch.org/), an international network aiming at a systematic evaluation of the HLA genotype as a possible cancer risk modifier in LS. Here we summarize the current knowledge on the role of HLA type in cancer risk and outline future research directions to delineate possible association in the scenario of LS with genetically defined risk population and highly immunogenic tumors.

Keyword(s): HLA genotype ; Lynch syndrome ; cancer immunoediting ; immune surveillance ; personalized cancer risk

Note: #EA:F210#LA:F210# / 2023 May 15;152(10):2024-2031

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Contributing Institute(s):

1. KKE Angewandte Tumorbiologie (F210)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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