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.
Barbera-Guillem
E
E
BioCrystal Ltd., Westerville, OH 43082-8888, USA.
Nelson
M B
MB
Barr
B
B
Nyhus
J K
JK
May
K F
KF
Feng
L
L
Sampsel
J W
JW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008212:Lymphocyte Depletion; D015674:Mammary Neoplasms, Animal; D008546:Melanoma, Experimental; D051379:Mice; D010641:Phenotype; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D000069283:Rituximab