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Flow cytometric analysis of B & T-lymphocyte phenotypes in breast cancer (CFS control group), 2020, Strachan (M.D. Thesis)

Discussion in 'ME/CFS research' started by Dolphin, May 10, 2022.

  1. Dolphin

    Dolphin Senior Member (Voting Rights)

    Messages:
    4,990
    From: Dr. Marc-Alexander Fluks

    Source: University of Leeds
    Date: May 2020, online January 11, 2022
    URL: https://etheses.whiterose.ac.uk/28168/

    https://etheses.whiterose.ac.uk/28168/1/Final and corrected MD C.Strachan.pdf


    A flow cytometric analysis of B and T-lymphocyte phenotypes in breast
    cancer: implications for prognosis, treatment and recovery
    ---------------------------------------------------------------------
    Caroline Louise Strachan
    - Faculty of Medicine and Health, University of Leeds, U.K.


    Abstract

    Introduction:
    It is widely understood that the T-lymphocyte is closely linked to
    prognosis and treatment response in certain solid organ malignancies
    including breast. B-Lymphocytes have, however, received comparatively
    little attention in this field and it remains unclear what role, if any,
    B-lymphocyte subtypes play in carcinogenesis or prognosis in breast
    cancers. Likewise, it is unknown what effect systemic treatments such as
    chemotherapy have on B-cell immunity, or the role these lymphocyte
    subtypes may have in the side-effect profile of such therapies. Cancer
    related fatigue (CRF) is one such side-effect of cancer and its
    treatments, the pathogenesis of which has been linked to impaired
    immunity including altered lymphocyte phenotypes.
    My aim in this work was to perform detailed phenotypical analyses of B-
    and Tlymphocytes in breast cancer, as well as phenotypical alterations
    driven by cancer treatments, to provide insight into the function of
    B-lymphocytes in this disease process, adding to the growing body of
    knowledge driving immunotherapeutic development.

    Methods
    43 primary breast cancer patients, scheduled to receive adjuvant
    chemotherapy, were recruited following resection surgery alongside 10
    age- and sex-matched healthy controls. 27 Chronic fatigue syndrome (CFS)
    patients were recruited at diagnosis, as a comparator group for
    assessments relating to CRF
    . 15 further patients with primary breast
    cancer were recruited prior to resection surgery for analyses of fresh
    tumour tissue and peripheral blood. Phenotypes of circulating
    lymphocytes were analysed using multicolour flow cytometry at various
    time-points in the larger breast cancer cohort and its associated
    comparator groups (CFS and healthy controls), along with general health
    and well-being screening questionnaires as used in the diagnosis of CFS.
    For the fresh tissue study, tumour tissue was biopsied and analyses of
    tissue-resident B- and T-lymphocytes were performed, along with
    circulating analyses as previously, focusing on regulatory B and T
    subtypes. Results were analysed using paired T-tests, 2-way ANOVA, and
    correlation analysis.

    Results
    Lymphocyte phenotype was vastly altered by chemotherapy. Within the
    Tcell pool, the naïve subset is diminished with proportional increases
    to the memory cell pool and the overall expansion of HLA-DR surface
    expression on CD4+ T-cells. Regulatory T-cells were unchanged. Within
    the B-cell pool, memory cells were 5 largely reduced by chemotherapy,
    the resulting phenotype being naïve and transitional dominant.
    Pro-inflammatory cytokine expression by regulatory B-cells was
    diminished, yet IL-10 expression remains unchanged.
    The CD20+CD27+ regulatory Memory B-cell subset is demonstrated as a
    critical Bcell phenotype in breast cancer prognosis and in fatigue.
    CD27+ regulatory memory B-cell dominates the phenotype in tumour tissue
    where these subsets, in addition to naïve T-cells, correlated
    positively with poor prognostic indicators in breast cancer both in
    peripheral blood and tumour tissue. Additionally, expression of effector
    regulatory cytokines IL-10 and TNF-alpha from the memory B-cell subsets
    correlated with prognosis and fatigue.

    Conclusions
    Detailed B-lymphocyte phenotypes have been clearly demonstrated in
    breast cancer and in fatigue, with the regulatory CD20+CD27+ memory
    B-cell subset prevailing as the dominant cell type relating to breast
    cancer prognosis, both in tumour and peripheral blood, as well as
    fatigue scores. This first insight into the phenotype and function of
    B-cells and B-regs in breast cancer highlights the memory B-cell subset
    as a driver in the pathogenesis of this disease, and provides a target
    for further research and potential novel lines of investigation in the
    on-going search for immunotherapies.

    --------
    (c) 2020 University of Leeds
     
  2. Trish

    Trish Moderator Staff Member

    Messages:
    51,881
    Location:
    UK
    It's hard to tell from this abstract what role the CFS control group played in this research, since no data is given from them. I am guessing all they did was to fill in a fatigue questionnaire as a basis for comparison with the fatigue in the cancer patients during and after chemotherapy.
     
    MEMarge likes this.
  3. Dolphin

    Dolphin Senior Member (Voting Rights)

    Messages:
    4,990
    The full text is available for free at the link for anyone wanting more info (and had free energy/time/etc.).
     
    MEMarge and Trish like this.

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