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1.
Breast Cancer Res ; 18(1): 10, 2016 Jan 26.
Article in English | MEDLINE | ID: mdl-26810608

ABSTRACT

BACKGROUND: Approximately 30 % of breast cancer patients receive chemotherapy, yet little is known about influences of current regimens on circulating lymphocyte levels and phenotypes. Similarly, clinico-pathological factors that modify these influences, and implications for future immune health remain mainly unexplored. METHODS: We used flow-cytometry to assess circulating lymphocyte levels and phenotypes in 88 primary breast cancer patients before chemotherapy and at time-points from 2 weeks to 9 months after chemotherapy completion. We examined circulating titres of antibodies against pneumococcal and tetanus antigens using ELISAs. RESULTS: Levels of B, T and NK cells were significantly reduced 2 weeks after chemotherapy (p < 0.001). B cells demonstrated particularly dramatic depletion, falling to 5.4 % of pre-chemotherapy levels. Levels of all cells recovered to some extent, although B and CD4(+) T cells remained significantly depleted even 9 months post-chemotherapy (p < 0.001). Phenotypes of repopulating B and CD4(+) T cells were significantly different from, and showed no sign of returning to pre-chemotherapy profiles. Repopulating B cells were highly depleted in memory cells, with proportions of memory cells falling from 38 % to 10 % (p < 0.001). Conversely, repopulating CD4(+) T cells were enriched in memory cells, which increased from 63 % to 75 % (p < 0.001). Differences in chemotherapy regimen and patient smoking were associated with significant differences in depletion extent or repopulation dynamics. Titres of anti-pneumococcal and anti-tetanus antibodies were both significantly reduced post-chemotherapy and did not recover during the study (p < 0.001). CONCLUSION: Breast cancer chemotherapy is associated with long-term changes in immune parameters that should be considered during clinical management.


Subject(s)
Antigens, CD/immunology , Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Lymphocyte Depletion , Lymphocytes/immunology , Adult , Aged , Antibodies/immunology , Antigens, CD/isolation & purification , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Breast Neoplasms/pathology , Female , Flow Cytometry , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Lymphocytes/pathology , Middle Aged , Streptococcus pneumoniae/immunology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Tetanus/immunology , Tetanus/microbiology
3.
J Clin Pathol ; 66(2): 146-50, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23172556

ABSTRACT

AIMS: Common variable immunodeficiency (CVID) is a primary antibody immunodeficiency with approximately 20% of patients reporting additional autoimmune symptoms. The primary aim of this study was to compare the levels of activated and regulatory T cells (Treg cells) in CVID patients in an attempt to clarify their possible interactions leading to the generation of autoimmunity. METHODS: Immunophenotyping of T cells was performed by flow cytometry using a whole blood approach. Surface expression of human leukocyte antigen HLA class II DR and intracellular levels of granzyme B in T cell subsets were assessed; Treg levels were measured using CD4 CD25, FOXp3 and CTLA-4. RESULTS: CVID patients had higher levels of granzyme B and HLA-DR on CD8(+) T cells compared with control values (mean of 59% vs 30% and 45% vs 21%, respectively). Patients also had reduced levels of Treg cells compared with control values (con mean=3.24% vs pat=2.54%). Patients with autoimmunity (5/23) had a similar level of T cell activation markers to the rest of the patients but with lower Treg cells (mean of 1.1%) and reduced CD25 and CTLA-4 expression. Patients with autoimmunity had a higher ratio of activated to Treg cells compared with patients with no autoimmune symptoms. CONCLUSIONS: These results highlight that reduced levels of Treg cells were associated with elevated levels of activated T cells, suggesting that reduced Treg cells in these patients may have functional consequences in allowing exaggerated T cell responses.


Subject(s)
Autoimmunity , Common Variable Immunodeficiency/enzymology , Common Variable Immunodeficiency/immunology , Granzymes/analysis , HLA-DR Antigens/analysis , T-Lymphocyte Subsets/enzymology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Biomarkers/analysis , CD8-Positive T-Lymphocytes/enzymology , CD8-Positive T-Lymphocytes/immunology , CTLA-4 Antigen/analysis , Case-Control Studies , Female , Flow Cytometry , Forkhead Transcription Factors/analysis , Humans , Immunophenotyping/methods , Interleukin-2 Receptor alpha Subunit/analysis , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged , Up-Regulation
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