Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Abstract

Purpose We investigated the antitumor reactivity of adoptively transferred effector B cells and the mechanisms by which they may mediate tumor regression in a spontaneous metastases model. Experimental Design 4T1 breast cancer cells were inoculated into the flanks of syngeneic Balb/C mice to prime draining lymph nodes. Tumor-draining lymph nodes (TDLN) were harvested and B cells activated ex vivo with LPS and anti-CD40 mAb. These activated B cells were adoptively transferred into mice inoculated with 4T1 tumor in the mammary fat pad. The induction of host T cell immunity was evaluated. Results Activated 4T1 TDLN B cells secreted IgG in response to tumor cells which was immunologically specific. These activated B cells were capable of mediating specific lysis of tumor cells in vitro. Transfer of these activated B cells alone mediated the inhibition of spontaneous metastases to the lung. Examination of the host revealed that the transfer of these B cells resulted in the induction of tumor specific T cell immunity as measured by cytotoxicity and cytokine (IFNγ and GM-CSF) production. The combined transfer of activated T and B cells from TDLN resulted in tumor regression, which was greater than either cell population alone, with host B cells capable of producing IgG that mediated lysis of tumor in the presence of complement. Conclusions We have found that appropriately primed B cells can mediate tumor regression by itself and confers host T cell antitumor immunity. Furthermore, effector B cells can serve as a useful adjunct in adoptive T cell therapy.

CD20+ Tumor-Infiltrating Lymphocytes Have an Atypical CD27− Memory Phenotype and Together with CD8+ T Cells Promote Favorable Prognosis in Ovarian Cancer

“…Thus, it may be possible to generate more potent, sustained T-cell responses in the tumor environment by promoting the infiltration of tumor-reactive B cells. In support of this idea, adoptive transfer of activated B cells has been shown to induce tumor-specific T-cell immunity in murine models (54). Thus, improved understanding of the functional phenotype of CD20 þ TIL, their target antigens, and their mechanism of recruitment to target tissues may facilitate the design of more effective immunotherapies for the treatment of cancer.…”

Fludarabine, cyclophosphamide, and multiple‐dose rituximab as frontline therapy for chronic lymphocytic leukemia

“…B-cells have been shown to exert anti-tumor effects through both antibody-mediated cytotoxicity of malignant cells and antigen-presentation to effector T-cells. 27, 28 It is therefore feasible that the immunosuppressive and B-cell depleting effects of rituximab might impair immune surveillance and predispose to secondary malignancies. Alternatively, rituximab might potentiate the cytotoxic effect of the backbone FC chemotherapy on normal hematopoietic progenitors and predispose to secondary hematologic malignancies.…”

B Cell-Based Cancer Immunotherapy

“…In two studies, which applied RNA-transfected or OVA antigen-pulsed CD40B cells in a therapeutic setting, treatment did not result in delayed tumor growth of B16.F10 melanomas or E.G7 lymphomas, respectively [71, 72]. In two studies, B cells were isolated from tumor-draining lymph nodes (TDLN) of wild-type mice with MCA205, D5G6, or 4T1 tumors [73, 74]. After activation with anti-CD40 antibodies, they were adoptively transferred into syngeneic tumor-bearing mice.…”