Collapse of the CD27+ B-cell compartment associated with systemic plasmacytosis in patients with advanced melanoma and other cancers.

Abstract

PURPOSE:

Disturbed peripheral blood B-cell homeostasis complicates certain infections and autoimmune diseases, such as HIV and systemic lupus erythematosus, but has not been reported in cancer. This study aimed to investigate whether B-cell physiology was altered in the presence of melanoma and other cancers.

EXPERIMENTAL DESIGN:

Flow cytometry was used to identify phenotypic differences in B cells from patients with melanoma and normal donors. In vitro stimulated B cells were assessed for responsiveness and also used as stimulators of allogeneic T cells in mixed lymphocyte reactions.

RESULTS:

We show B-cell dysregulation in patients with advanced melanoma (n = 26) and other solid tumors (n = 13), marked by a relative and absolute loss of CD27+ (memory) B cells and associated with an aberrant systemic plasmacytosis. Functionally, B cells from patients with melanoma inefficiently up-regulated immunoregulatory molecules and weakly secreted cytokines in response to CD40 and toll-like receptor 9 agonists. Stimulated B cells from patients induced proliferation of alloreactive CD4+ T cells, but these T cells poorly secreted IFNgamma and interleukin-2. These effects were recapitulated by using purified normal donor CD27(neg) B cells in these same assays, linking the predominance of CD27(neg) B cells in patients with the observed functional hyporesponsiveness. Indeed, B-cell dysfunction in patients strongly correlated with the extent of loss of CD27+ B cells in peripheral blood.

CONCLUSIONS:

Disturbed B-cell homeostasis is a previously unrecognized feature of patients with advanced melanoma and other cancers and may represent an unanticipated mechanism of immune incompetence in cancer.

• Authors: Erica L Carpenter, Rosemarie Mick, Andrew J Rech, Gregory L Beatty, Theresa A Colligon, Myrna R Rosenfeld, David E Kaplan, Kyong-Mi Chang, Susan M Domchek, Peter A Kanetsky, Leslie A Fecher, Keith T Flaherty, Lynn M Schuchter, Robert H Vonderheide
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 13 Pg. 4277-87 (Jul 01 2009) ISSN: 1557-3265 [Electronic] United States
• PMID: 19549767 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• IL2 protein, human
• Interleukin-2
• Tumor Necrosis Factor Receptor Superfamily, Member 7
• Interferon-gamma

Topics

• Adult
• Apoptosis (immunology)
• B-Lymphocytes (metabolism, pathology, physiology)
• CD4-Positive T-Lymphocytes (immunology, metabolism, pathology, transplantation)
• Disease Progression
• Humans
• Interferon-gamma (metabolism)
• Interleukin-2 (metabolism)
• Lymphocyte Activation (immunology)
• Lymphocyte Count
• Melanoma (complications, immunology, pathology)
• Neoplasms (complications, immunology)
• Plasma Cells (metabolism, pathology)
• Transplantation, Homologous
• Tumor Escape (immunology)
• Tumor Necrosis Factor Receptor Superfamily, Member 7 (metabolism)