The absence of B lymphocytes reduces the number and function of T-regulatory cells and enhances the anti-tumor response in a murine tumor model

Increasing evidence suggests that B lymphocytes play a central role in inhibiting the immune response against certain tumors, but the underlying mechanisms by which B cells facilitate tumor growth are still poorly understood. In this study, we investigated how the presence or absence of B cells affe...

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Vydané v:Cancer Immunology, Immunotherapy Ročník 60; číslo 5; s. 609 - 619
Hlavní autori: Tadmor, Tamar, Zhang, Yu, Cho, Hyun-Mi, Podack, Eckhard R., Rosenblatt, Joseph D.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Berlin/Heidelberg Springer-Verlag 01.05.2011
Springer Nature B.V
Predmet:
Animals
Antibodies
Antibodies, Monoclonal - immunology
B-Lymphocytes - immunology
Cancer
Cancer Research
CD4 Antigens - analysis
Cell Line, Tumor
Cell Proliferation
Cells
Female
Flow Cytometry
Forkhead Transcription Factors - analysis
Immunology
Immunophenotyping
Interleukin-2 Receptor alpha Subunit - analysis
Lymphatic system
Lymphocyte Count
Lymphocyte Depletion
Lymphocytes
Mammary Neoplasms, Experimental - immunology
Mammary Neoplasms, Experimental - pathology
Medicine
Medicine & Public Health
Mice
Mice, Inbred BALB C
Mice, Knockout
Neoplasm Transplantation
Oncology
Original
Original Article
Spleen
T-Lymphocytes - immunology
T-Lymphocytes, Regulatory - immunology
United States > US
B lymphocyte
T-regulatory cells (T-reg)
Immune-competent mice (ICM)
B-cell-deficient mice (BCDM)
Anti-tumor immunity
ISSN:0340-7004, 1432-0851, 1432-0851
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Shrnutí:Increasing evidence suggests that B lymphocytes play a central role in inhibiting the immune response against certain tumors, but the underlying mechanisms by which B cells facilitate tumor growth are still poorly understood. In this study, we investigated how the presence or absence of B cells affects expansion and function of T-regulatory cells (‘T-regs’) in a murine breast tumor model (EMT-6). We compared tumor growth, and the number and function of T-reg cells in wild-type immune-competent mice (ICM) and B-cell-deficient mice (BCDM). Mice were either tumor-naive or implanted with EMT-6 mammary adenocarcinoma cells. Tumor growth was markedly inhibited in BCDM, compared to wild-type mice (ICM). Increased T-reg expansion as defined by CD4+/CD25+/FOXP3+ cells was evident following EMT-6 inoculation in ICM in comparison with non-tumor-bearing mice or compared to BCDM in which tumor had been implanted. The percentage and absolute number of T-regs in the spleen, tumor draining lymph nodes, and tumor bed were significantly reduced in BCDM compared to ICM. T-reg function, measured by suppression and proliferation assays, was also reduced in tumor inoculated BCDM compared to ICM. Our studies indicate that absence of B cells may play a role in augmenting the T-cell anti-tumor response, in part due to effects on T-regulatory cell expansion and function.
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ISSN:0340-7004
1432-0851
1432-0851
DOI:10.1007/s00262-011-0972-z