Lewis Lung Carcinoma-derived CCL22 recruitment of T regulatory cells (B148)

Abstract

Abstract Two aspects of cancer progression that contribute to malignancy are the ability of the tumor to metastasize to remote locations in the body, and the ability to evade effective host anti-tumor immune responses. It has been shown that T regulatory cells (Treg) can inhibit immune effector cell function and aid in anti-tumor immune evasion. Several types of tumors have elevated Treg numbers, and it is believed that tumors may actively recruit these cell types. Treg migration is induced by several chemokines and their receptors such as CCL22 and CCR4. Here, we use flow cytometry to analyze CCR4 expression on T cell populations and show that Tregs express more CCR4 than any other T-cell type. We also used ELISA to compare CCL22 secretion levels in normal and Lewis Lung Carcinoma (LLC) bearing lung tissue. While high basal levels of CCL22 are secreted from normal lung tissue, even higher levels are secreted by LLC bearing lung tissue. In addition, we used media conditioned on these tissues in transwell migration assays to measure preferential Treg chemoattraction. Normal lung tissue induced high levels of selective Treg chemoattraction, while LLC bearing lung selectively attracted even greater numbers of Tregs. These data suggest that normal lung tissue may be able to recruit elevated levels of immune inhibitory Tregs through the secretion of CCL22 prior to metastasis, and that once LLC metastasis occurs, both CCL22 and Treg levels increase even further.