CCL21 is a small cytokine that binds to the chemokine receptor CCR7. It is thought to inhibit haemopoiesis and stimulate chemotaxis, in vitro antibody studies having shown CCL21 to be selectively chemotactic for activated T-cells and thymocytes. It may also have a role in lymphocyte migration to secondary lymphoid organs. We at Novus Biologicals have nine CCL21 antibodies on our antibody database.
Tumour growth is dependent on the cells’ ability to evade attack by the host’s immune system. In 2007, G.A Rabinovich et al published a paper suggesting tumour cells employ a number of strategies for this, including activation of negative regulatory pathways and secretion of immunosuppressive agents. In the same year, Shields et al published a paper showing CCL21 to be secreted by certain tumour cells. Now, they have published a new study showing a novel mechanism by which CCL21-secreting cells actively alter their outer morphology, presenting a lymphoid-like surface that promotes evasion of the immune response by creating a tolerant stromal microenvironment.
Using a shRNA (small hairpin RNA) and lentiviral transduction techniques, mouse melanoma cell sublines were created expressing varying amounts of CCL21. CCL21 secretion was either upregulated (CCL21+) down regulated (CCL21-) or left unchanged as a control. The resultant sublines were then transplanted into normal syngeneic mice. Examination of the resultant tumours revealed that CCL21+ tumours were markedly larger than those from the CCL21- group. Furthermore, CCL21-secreting tumours had reorganised their microenvironment to resemble lymphoid tissue.
Several factors pointed to this. Firstly, LTi (lymphoid tissue-induced) cells were found in all tumours except those expressing low CCL21 levels. LTi cells are integral to normal lymphoid tissue, promoting localised expression of chemokines from stromal cells such as FRCs (fibroblast-like reticular cells). Additionally, antibody assays indicated the presence of gp38, ER-TR7 and PNAd stromal lymphoid cell markers in the stroma of CCL21+ tumours, but not those of CCL- lines.
Although lymphoid tissue is associated with activation of the immune response, it is also known to suppress it under normal conditions. The CCL21-secreting tumours recruited immune suppressors associated with normal lymphoid tissue; further CCL21 antibody research will examine the pathways involved. Our antibody catalogue at Novus Biologicals is often used for immune response research.