Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases

Magdalena Wójcik; Ulana Juhas; Elyas Mohammadi; Jonas Mattisson; Kinga Drężek-Chyła; Edyta Rychlicka-Buniowska; Bożena Bruhn‐Olszewska; Hanna Davies; Katarzyna Chojnowska; Paweł Olszewski; Michał Bieńkowski; Michał Jankowski; Olga Maria Rostkowska; Andrzej Rafal Hellmann; Rafał Pęksa; Jacek Kowalski; Marek Zdrenka; Jarek Kobiela; Wojciech Zegarski; Wojciech Biernat; Łukasz Szylberg; Piotr Remiszewski; Jakub Mieczkowski; Natalia H. Filipowicz; Jan Piotr Dumanski

doi:10.1038/s41598-024-60049-y

Genetic & Genomic MedicineScientific ReportsApr 24, 2024

Peer-reviewed journal article

Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases

Magdalena Wójcik iD, Ulana Juhas iD, Elyas Mohammadi iD, Jonas Mattisson iD, Kinga Drężek-Chyła iD, Edyta Rychlicka-Buniowska iD, Bożena Bruhn‐Olszewska iD, Hanna Davies iD, Katarzyna Chojnowska iD, Paweł Olszewski iD, Michał Bieńkowski iD, Michał Jankowski iD, Olga Maria Rostkowska iD, Andrzej Rafal Hellmann iD, Rafał Pęksa iD, Jacek Kowalski iD, Marek Zdrenka, Jarek Kobiela iD, Wojciech Zegarski, Wojciech Biernat iD, Łukasz Szylberg iD, Piotr Remiszewski iD, Jakub Mieczkowski iD, Natalia H. Filipowicz iD, Jan Piotr Dumanski iD

Abstract

Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4+ T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY-cells (22%) in comparison to CD4+ T-lymphocytes and cytotoxic CD8+ T-lymphocytes. Using scRNA-seq LOY was also linked to higher expression of PDCD1, TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.

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