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Am J Pathol. 2014 Nov;184(11):3120-9. doi: 10.1016/j.ajpath.2014.07.003. Epub 2014 Aug 28.

B cells promote tumor immunity against B16F10 melanoma.

Author information

1
Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan.
2
Department of Dermatology, University of Fukui, Fukui, Japan.
3
Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
4
Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan. Electronic address: t-matsushita@med.kanazawa-u.ac.jp.

Abstract

B cells are known to be critical mediators of tumor immunity; however, the mechanisms through which they exert this function remain unclear. B-cell linker protein (BLNK) is an essential component of the B-cell antigen receptor signaling machinery and is required for B-cell development, as evidenced by BLNK-deficient (BLNK(-/-)) mice, in which the development and function of B cells are severely impaired. Herein, we evaluated the role of B cells in the development of tumor immunity against B16F10 melanoma using BLNK(-/-) mice. B16F10 melanoma grew more aggressively in BLNK(-/-) mice, resulting in a twofold increase in tumor volume compared with wild-type mice. As predicted, tumor-infiltrating B-cell numbers were decreased in BLNK(-/-) mice. Paradoxically, tumor-infiltrating T-cell numbers were decreased in BLNK(-/-) mice, although inguinal lymph node T-cell numbers were increased. Adoptive transfer of B cells from wild-type mice into BLNK(-/-) mice attenuated B16F10 melanoma growth, with increasing numbers of B and T cells infiltrating into tumors. In addition, percentages of interferon-γ- and tumor necrosis factor-α-producing tumor-infiltrating T cells were restored. Taken together, our study supports the concept that B cells enhance tumor immunity against B16F10 melanoma by promoting T-cell infiltration into tumors and cytokine production within the tumor microenvironment.

PMID:
25173132
DOI:
10.1016/j.ajpath.2014.07.003
[Indexed for MEDLINE]

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