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

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.

Promotion of tumor invasion by cooperation of granulocytes and macrophages activated by anti-tumor antibodies.

We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.