B lymphocyte pathology in human colorectal cancer. Experimental and clinical therapeutic effects of partial B cell depletion

Abstract

Accumulating data are showing that the humoral immune response against tumors could favor tumor progression. However, no B lymphocyte pathology has been reported in cancer. Using anti-IgM Ab we nonspecifically depleted B cells in tumor-bearing mice, a treatment that resulted in significant reduction of tumor burden. We analyzed the B lymphocyte phenotype of abdominal lymph nodes and peripheral blood from advanced colon cancer patients by flow cytometry, and compared the B cell phenotype with that found in samples from normal donors. In both lymph nodes and peripheral blood of cancer patients, abnormal populations of B lymphocytes appeared that express an increased CD21 and/or sTn antigens on their cell surface. All patients showed a reduction of CD19+ cells. In a limited clinical test, we analyzed the effects of a partial B cell depletion with Rituximab. The treated patients did not develop any side-effects; the CD21-hyperpositive lymphocytes were reduced, but the proportion of sTn-positive lymphocytes remained unaffected. Apparent reduction of the tumor burden was reported in 50% of the patients when the treatment was ended.

A Single Dose of Rituximab Does Not Deplete B Cells in Secondary Lymphoid Organs but Alters Phenotype and Function

“…The observed persistence of B cells in lymphoid tissues after RTX treatment, has been reported by others before (8,13,15,(22)(23)(24)(25)(26). However, in contrast to our finding of unaffected numbers of LN B cells, these studies described at least some degree of B cell reduction in synovial tissue, spleen or LNs.…”

Increased rejection of primary tumors in mice lacking B cells: Inhibition of anti-tumor CTL and TH1 cytokine responses by B cells

“…In a syngeneic mouse model, pro-active B cell depletion of tumor-bearing mice led to reduction in tumor burden. 41 It is of interest to examine whether this phenomenon could be applied to a variety of tumors. Rituximab, a humanized anti-CD20 antibody extensively used for treating B cell lymphomas produces a state of B-cell depletion lasting several months and could be used for the purpose of adult B cell depletion in humans.…”

CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes

“…For example, studies comparing wild-type and B cell-deficient mice found that B cells inhibit T cell-mediated regression of established tumors (32,33), as well as T cell responses to cancer vaccines (34)(35)(36). B cells can impair the priming of CD8 + CTL responses by CD4 + T cells and instead promote nonprotective humoral immune responses (37).…”