CD40-activated B cells contribute to mesothelioma tumor regression

Immunology and Cell Biology
Connie JackamanDelia J Nelson

Abstract

Targeting CD40, a member of the tumor necrosis factor superfamily, using agonist antibodies (Abs) produces dramatic antitumor effects. Indeed, high-dose intravenous anti-CD40 Ab 'licenses' dendritic cells (DCs) that instruct activated CD8(+) cytotoxic T cells to leave lymph nodes (LNs) and penetrate the mesothelioma tumor microenvironment. However, toxic side effects and the potential of an 'overwhelmed' immune response warrant an alternative approach. In this study, we show that injecting lower doses of anti-CD40 Ab directly into the tumor bed avoided toxic side effects and prolonged survival in 60% of mice, with most cured. Unexpectedly, DCs in tumors and LNs 'disappeared', CD8(+) tumor-specific T-cell numbers and function were not enhanced, and T cells did not infiltrate regressing tumors. CD4(+) or CD8(+) depletion only marginally hindered anti-CD40 Ab efficacy implying another effector mechanism. B-cell numbers significantly increased in tumors, draining LNs and spleens during intratumoral anti-CD40 Ab treatment. CD40 targeting had no effect on splenic B-1 cells, obliterated marginal zone B cells and promoted follicular (FO) B-cell activity. Adoptive transfer of tumor antigen-experienced, CD40-activated B cells, or their i...Continue Reading

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Feb 23, 2012·International Immunology·Connie JackamanDelia J Nelson
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