Tumor-secreted products repress B-cell lymphopoiesis in a murine model of breast cancer.
Growing cancers are known to modify immune responses through suppressive mechanisms manifested within the local tumor microenvironment. Accumulating evidence indicates that secreted tumor products can also influence on distant immunological compartments, including myelopoiesis in the bone marrow. However, it is unknown if a similar effect can occur to regulate B-cell lymphopoiesis in breast cancer. Examining the MMTV-PyMT murine model of breast cancer, we show a complete block in bone marrow B-cell lymphopoiesis, which is dependent on tumor burden. We also observed an increase in the total number of splenic B cells and an elevated frequency of marginal zone B cells. By using in vitro assays of B-cell lymphopoiesis, we show that tumor-secreted molecules directly inhibit B-cell progenitor proliferation and favor maturation. These data demonstrate a profound sensitivity of B-cell lymphopoiesis to the accumulation of ectopically produced molecules during tumor growth in PyMT.
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Joshua M
JM
Moreau
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Michael
M
Mielnik
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Alexandra
A
Berger
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Caren
C
Furlonger
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Christopher J
CJ
Paige
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology*; D001943:Breast Neoplasms / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D038041:Lymphopoiesis; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D047368:Tumor Burden; D019139:Tumor Escape; D059016:Tumor Microenvironment
D000957:Antigens, Viral, Tumor
B cells; Breast cancer; Hematopoiesis; Lymphopoiesis; MMTV-PyMT; PyMT