| 1. |
- Dumanski, Jan P., et al.
(author)
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Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
- 2021
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 78:8, s. 4019-4033
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Journal article (peer-reviewed)abstract
- Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer’s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a “genetic wasteland”, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.
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| 2. |
- Sieminska, Izabela, et al.
(author)
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The Level Of Myeloid Derived-Suppressor Cells In Peripheral Blood Of Patients With Prostate Cancer After Various Types Of Therapy
- 2020
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In: Polish Journal of Pathology. - 1233-9687 .- 2084-9869. ; 71:1, s. 46-54
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Journal article (peer-reviewed)abstract
- Prostate cancer is one of the most frequent cancers in men. Although several treatment options exist, their clinical effectiveness is still not satisfactory. One the possible reason of such situation might be the presence of myeloid-derived suppressor cells (MDSC) and their pro-turnorigenic activity. MDSC possess irnmunosuppressive ability and in many studies were shown to support tumor development and progression. In this study we addressed the question whether commonly used therapies of prostate cancer affect the level of MDSC populations in the patients' blood. We compared the level of granulocytic (Gr-MDSC), monocytic (Mo-MDSC) and early stage MDSC (eMDSC) in the blood of patients at different clinical stage and different tumor grading scores, who underwent either surgery or hormonal therapy alone or were given a combined treatment, including e.g. radiotherapy. The obtained results showed that the level of Gr-MDSC was significantly lower in all treated patients comparing to untreated group. On the other hand, surgery or hormonal therapy alone did not affect the level of Mo-MDSC. These results were independent of the PSA level, the tumor grading and clinical stage of the patients. In conclusion, we suggest that Mo-MDSC should be considered as a potential therapy target in the course of prostate cancer treatment to enhance its anti-tumor effectiveness.
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