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Myeloid-derived suppressor cell subtypes differentially influence T-cell function, T-helper subset differentiation, and clinical course in CLL
- Ferrer, G (author)
- Jung, B (author)
- Chiu, PY (author)
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- Aslam, R (author)
- Palacios, F (author)
- Mazzarello, AN (author)
- Vergani, S (author)
- Bagnara, D (author)
- Chen, SS (author)
- Yancopoulos, S (author)
- Xochelli, A (author)
- Yan, XJ (author)
- Burger, JA (author)
- Barrientos, JC (author)
- Kolitz, JE (author)
- Allen, SL (author)
- Rai, KR (author)
- Sherry, B (author)
- Chiorazzi, N (author)
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- (creator_code:org_t)
- 2021-05-02
- 2021
- English.
- In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:11, s. 3163-3175
- Journal article (peer-reviewed)
Abstract
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- Cancer pathogenesis involves the interplay of tumor- and microenvironment-derived stimuli. Here we focused on the influence of an immunomodulatory cell type, myeloid-derived suppressor cells (MDSCs), and their lineage-related subtypes on autologous T lymphocytes. Although MDSCs as a group correlated with an immunosuppressive Th repertoire and worse clinical course, MDSC subtypes (polymorphonuclear, PMN-MDSC, and monocytic, M-MDSCs) were often functionally discordant. In vivo, PMN-MDSCs existed in higher numbers, correlated with different Th-subsets, and more strongly associated with poor clinical course than M-MDSCs. In vitro, PMN-MDSCs were more efficient at blocking T-cell growth and promoted Th17 differentiation. Conversely, in vitro M-MDSCs varied in their ability to suppress T-cell proliferation, due to the action of TNFα, and promoted a more immunostimulatory Th compartment. Ibrutinib therapy impacted MDSCs differentially as well, since after initiating therapy, PMN-MDSC numbers progressively declined, whereas M-MDSC numbers were unaffected, leading to a set of less immunosuppressive Th cells. Consistent with this, clinical improvement based on decreasing CLL-cell numbers correlated with the decrease in PMN-MDSCs. Collectively, the data support a balance between PMN-MDSC and M-MDSC numbers and function influencing CLL disease course.
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- By the author/editor
- Ferrer, G
- Jung, B
- Chiu, PY
- Aslam, R
- Palacios, F
- Mazzarello, AN
- show more...
- Vergani, S
- Bagnara, D
- Chen, SS
- Yancopoulos, S
- Xochelli, A
- Yan, XJ
- Burger, JA
- Barrientos, JC
- Kolitz, JE
- Allen, SL
- Stamatopoulos, K
- Rai, KR
- Sherry, B
- Chiorazzi, N
- show less...
- Articles in the publication
- Leukemia
- By the university
- Karolinska Institutet
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