B Cells Promote Tumor Immunity against B16F10 Melanoma

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.

Cross-platform comparison of independent datasets identifies an immune signature associated with improved survival in metastatic melanoma

“…However, B cells are prominent players in autoimmunity and tissue rejection [ 30 ], implying their role in breaking tolerance, a key event in successful anti-tumor immunity [ 31 ]. Consistent with these findings, animal models of B cell deficiency show more aggressive growth of B16F10 melanoma, which can be ameliorated with adoptive B cell transfer [ 32 , 33 ]. In these models, B cells seem to promote T cell infiltration and cytokine production within the tumor.…”

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…In a mouse model of B16 melanoma, DiLillo et al demonstrated that B-cell depletion was associated with faster tumor growth, increased lung metastasis, and decreased numbers of both CD4 + and CD8 + effector T cells (DiLillo, Yanaba, & Tedder, 2010). These observations were confirmed by Kobayashi et al in B-cell linker protein (BLNK)-deficient mice, another model of B-cell deficiency considered more relevant than μMT mice (Hayashi et al, 2000;Jumaa et al, 1999;Kobayashi et al, 2014;Minegishi et al, 1999;Pappu et al, 1999). In parallel, numerous clinical studies have demonstrated that a high density of B cells within the TME is associated with increased patient survival, for instance in CRC (Bindea et al, 2013).…”

Role of immune cells in pancreatic cancer from bench to clinical application

“…There are conflicting reports showing TIL-Bs have tumor-protective or tumor-promoting function. [145,146] TIL-Bs have been reported to be prevalent in human PC tissues. Gunderson et al [147] demonstrated human PC show increased expression of CD20 and immunoglobulin compared with normal pancreas.…”