PhD Scientific Days 2026

Molecular Medicine 3.

Decoding Cytokine-Stroma Interactions in Colorectal Cancer: Fibroblasts Overshadow IL-22 while Sparing IFNγ Function

Előadó neve

Dr. Hajdó, Szabolcs

Neptune code

UJWENK

Előadó munkahelye

Institute of Genetics, Cell- and Immunobiology

Előadó telefonszáma

+36206701431

Előadó e-mail címe

hajdo.szabolcs@semmelweis.hu

Az előadás címe

Decoding Cytokine-Stroma Interactions in Colorectal Cancer: Fibroblasts Overshadow IL-22 while Sparing IFNγ Function

Szerző(k) neve és munkahelye

Szabolcs Hajdó¹, Zsolt Komlósi¹, Barbara Molnár-Érsek¹, Idan Carmi¹, Zoltán Wiener¹

1: Institute of Genetics, Cell- and Immunobiology

Bemutatás módja

Szóbeli

Szekció

Molecular Medicine 3.

Language of the presentation

English

Preferred session

Molecular Medicine

Összefoglaló szövege

Introduction:
Colorectal cancer (CRC) is the third most common malignancy worldwide and a leading cause of cancer-related mortality. It is characterized by a highly complex tumor microenvironment (TME), in which cancer-associated fibroblasts (CAFs) play a central role in regulating tumor growth and progression. In addition to CAFs, the TME contains a wide variety of immune cells, growth factors, and cytokines that interact in a tightly regulated and dynamic network.
Aims:
We aimed to determine how CAFs modulate the effects of immune cell-derived cytokines in the CRC microenvironment, specifically focusing on IL-22, a cytokine involved in epithelial barrier integrity, and IFNγ, an important effector cytokine of cytotoxic immune cells.
Methods:
Patient-derived CRC organoids (PDOs) were treated with IL-22 and IFN in the presence or absence of fibroblasts to assess colony formation, cell viability, and signaling pathways. As potential sources of IL-22, ILC3 cells were isolated from PBMC and co-cultured with PDOs. In parallel, fresh CRC samples were also processed to assess the distribution of ILC subsets within the tissue.
Results:
IL-22 stimulated the proliferation of PDOs through activation of the MAP kinase pathway and induced gene expression changes similar to those triggered by EGF. However, IL-22 did not influence fibroblast polarization. In co-cultures, PDOs induced IL-22 production in ILC3 cells, but not IL-17A, indicating that CRC organoids may selectively induce an IL-22-secreting ILC subset. Tumor tissues showed enrichment of ILC1 cells compared to PBMC. Treating PDOs with IFNγ resulted in partial tumor cell death. When co-culturing PDOs with fibroblasts, the protumorigenic effect of IL-22 on organoid formation was no longer apparent, as fibroblasts alone markedly enhanced organoid proliferation. Interestingly, the anti-tumoral effect of IFNγ was not influenced by fibroblasts.
Conclusions:
ILC3-derived IL-22 exerts protumorigenic effects in CRC, however, these are largely overshadowed by the pro-tumoral effects of fibroblasts in the TME. In contrast, IFNγ maintains its anti-tumor function independently of the presence of fibroblasts, highlighting distinct cytokine-stroma interactions.
Fundings: K137554, 2024-1.2.3-HU-RIZONT-2024-00003, TKP2021-EGA-24 (NRDI Office, Hungary), SE250+ PhD Scholarship to Sz.H. Ethical permission: TUKEB 2015, 51323-4/2015/EKU.

University

Semmelweis University

Supervisor

Prof. Zoltán Wiener

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem hagyta jóvá

Előadó

9047

Start

09:00

End

09:10