PhD Scientific Days 2026

Molecular Medicine 1.

Peripheral immune profiling indicates systemic immune activation in Lynch syndrome

Name of the presenter

Kelemen, István

Institute/workplace of the presenter

Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary

Authors

István Kelemen¹, Klaudia Horti-Oravecz¹, Patrícia Neuperger², Fanni Balogh³, Ágnes Kemény⁴, Dorottya Kövesdi⁵, Henriett Butz⁶, Attila Patócs⁷, Gábor János Szebeni⁸, Vince Kornél Grolmusz⁹
1: 1 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary 2 Lendület "Momentum" Hereditary Cancers Systems Biology Research Group, Hungarian Academy of Sciences - National Institute of Oncology, Budapest, Hungary 3 Doctoral School, Semmelweis University, Budapest, Hungary 4 Department of Oncology Biobank, National Institute of Oncology, Budapest, Hungary
2: Department of Rheumatology and Immunology, Albert Szent-Gyorgyi Medical School and Health Center, University of Szeged, Szeged, Hungary
3: 5 Laboratory of Functional Genomics, Core Facility, HUN-REN Biological Research Centre, Szeged, Hungary 6 Department of Rheumatology and Immunology, Albert Szent-Gyorgyi Medical School and Health Center, University of Szeged, Szeged, Hungary
4: Department of Physiology and Biochemistry, University of Veterinary Medicine Budapest, Budapest, Hungary
5: 8 Department of Immunology, Eötvös Loránd University, Budapest, Hungary
6: 1 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary 4 Department of Oncology Biobank, National Institute of Oncology, Budapest, Hungary 9 HUN-REN-NIO-TTK-HCEMM Oncogenomics Research Group, Budapest, Hungary 10 Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary
7: 1 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary 9 HUN-REN-NIO-TTK-HCEMM Oncogenomics Research Group, Budapest, Hungary 10 Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary
8: 5 Laboratory of Functional Genomics, Core Facility, HUN-REN Biological Research Centre, Szeged, Hungary 11 Department of Internal Medicine, Hematology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary
9: 1 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary 2 Lendület "Momentum" Hereditary Cancers Systems Biology Research Group, Hungarian Academy of Sciences - National Institute of Oncology, Budapest, Hungary 9 HUN-REN-NIO-TTK-HCEMM Oncogenomics Research Group, Budapest, Hungary

Text of the abstract

Introduction
Lynch syndrome (LS) is one of the most common hereditary cancer predisposition syndromes that significantly increases the risk of many types of cancer, especially colorectal and endometrial cancer. LS-associated mismatch repair deficient (dMMR) tumors often elicit local and systemic immune responses due to their high neoantigen profile, which is the basis of the efficacy of immune checkpoint inhibitor therapies.
Aims
Our study aimed to analyze the immunological landscape of LS.
Methods
We analyzed 199 participants, including 108 individuals with LS diagnosed at the National Institute of Oncology. The LS cohort comprised 44 presymptomatic carriers, 46 previously tumor-bearing but currently cancer-free individuals, 8 therapy-naive patients with active malignancy, and 10 patients receiving pembrolizumab (PD-1 inhibitor) treatment. The control group included 91 individuals with no confirmed hereditary cancer risk. Peripheral white blood cells were stained with a 30-marker Maxpar® DIP™ panel and measured on a Helios™ mass cytometer. Plasma concentrations of 13 cytokines were quantified using Luminex xMAP. Data were analyzed in R (v4.4.2) and GraphPad Prism.
Result
Representative sampling of 20 million cells and the analysis of median marker expression across 29 cell surface markers identified ten major immune populations. Three activated B cell subsets were elevated in untreated cancer patients accompanied by increased plasma IL-6, and less frequent in pembrolizumab-treated and cancer-free patients. Additionally, three naive subsets were enriched in pembrolizumab-treated and cancer-free individuals. Moreover, three antigen‑presenting cell populations – B cells, myeloid and plasmacytoid dendritic cells – showed high CCR7 expression in untreated cancer patients.
Conclusion
Our findings indicate a cancer‑associated immune phenotype in Lynch syndrome, suggesting coordinated alterations among potentially targetable immune cell populations that may contribute to a tolerogenic microenvironment and modulate therapeutic responsiveness.
Funding
Authors would like to acknowledge the financial support of the Lendület‑Momentum Program (LP2025‑21/2025), the National Research, Development and Innovation Office (NKFIH‑FK‑138377), the HUN‑REN Research Group Grant, and grants 2023‑1.1.1‑PIACI_FÓKUSZ‑2024‑00036, 2022‑1.2.6‑TÉT‑IPARITR‑2022‑00023, and 142877 FK22.