B cells are required for development of epithelial cancer associated with chronic inflammation

05/09/05

Chronic inflammation is linked to the development of certain types of cancer, but mechanisms mediating inflammation during premalignancy are not well understood. A new research study published in the May issue of Cancer Cell identifies B lymphocytes as important regulators of premalignancy associated with chronic inflammation. The results suggest that drugs targeted against B lymphocytes or recruitment of innate immune cells toward premalignant tissue may represent a viable strategy to protect against the development of cancer in tissues identified as "at risk" due to chronic inflammation.

Previous studies have implicated an interaction between adaptive immune cells, like B lymphocytes, and innate immune cells during chronic inflammatory diseases. Dr. Lisa M. Coussens and colleagues from the Cancer Research Institute at the University of California at San Francisco used a mouse model of inflammation-associated skin cancer to study the roles and interactions of these different white blood cells in the progression of cancer.

The mice used in the study, called HPV16 mice, developed premalignant skin that was characterized by infiltration of innate immune cells. Genetic elimination of T and B lymphocytes in this model system resulted in a failure to recruit innate white blood cells to premalignant skin and an absence of chronic inflammation. As a consequence, parameters of early cancer development were attenuated, and cancer incidence was significantly reduced. The researchers went on to show that transfer of B cells or even just serum from regular HPV16 mice into the lymphocyte-deficient HPV16 mice restored chronic inflammation in premalignant skin and reinstated mechanisms necessary for tumorigenesis, like blood vessel development (angiogenesis) and enhanced skin cell proliferation.

These findings support the idea that the adaptive immune system interacts with the innate immune system during cancer development. "Together, these data indicate that peripheral B cell activation is an essential step for early epithelial neoplastic development, and B cell-derived soluble mediators are necessary for establishing chronic inflammatory states that potentiate cancer development," explains Dr. Coussens. "Pharmacological interventions attenuating B cell activation or blocking B cell-mediated recruitment of innate immune cells may be effective in preventing premalignant progression."

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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