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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 (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq 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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1 Medical University of Gdańsk, 3P-Medicine Laboratory, Gdańsk, Poland (GRID:grid.11451.30) (ISNI:0000 0001 0531 3426)
2 Medical University of Gdańsk, 3P-Medicine Laboratory, Gdańsk, Poland (GRID:grid.11451.30) (ISNI:0000 0001 0531 3426); Medical University of Gdańsk, Department of Bioenergetics and Physiology of Exercise, Gdańsk, Poland (GRID:grid.11451.30) (ISNI:0000 0001 0531 3426)
3 Uppsala University, Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)
4 Medical University of Gdańsk, Department of Pathomorphology, Gdańsk, Poland (GRID:grid.11451.30) (ISNI:0000 0001 0531 3426)
5 Ludwik Rydygier’s Collegium Medicum, Bydgoszcz, Nicolaus Copernicus University, Surgical Oncology, Toruń, Poland (GRID:grid.5374.5) (ISNI:0000 0001 0943 6490); Oncology Center - Prof. Franciszek Łukaszczyk Memorial Hospital, Department of Surgical Oncology, Bydgoszcz, Poland (GRID:grid.5374.5)
6 Medical University of Gdańsk, Department of Oncological, Transplant and General Surgery, Gdańsk, Poland (GRID:grid.11451.30) (ISNI:0000 0001 0531 3426)
7 Oncology Center – Prof. Franciszek Łukaszczyk Memorial Hospital, Department of Tumor Pathology and Pathomorphology, Bydgoszcz, Poland (GRID:grid.11451.30)
8 Oncology Center – Prof. Franciszek Łukaszczyk Memorial Hospital, Department of Tumor Pathology and Pathomorphology, Bydgoszcz, Poland (GRID:grid.11451.30); Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Department of Clinical Pathomorphology, Bydgoszcz, Poland (GRID:grid.411797.d) (ISNI:0000 0001 0595 5584)
9 Medical University of Gdańsk, 3P-Medicine Laboratory, Gdańsk, Poland (GRID:grid.11451.30) (ISNI:0000 0001 0531 3426); Uppsala University, Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)