Cytokines and chemokines are key modulators of immune responses and play diverse roles in inflammatory diseases. Here, we discuss the role of specific cytokines and chemokines in cancer and tumor metastasis.
Chondrex Inc., is committed to enabling inflammatory research worldwide by providing a variety of animal models and detection assays for your study needs. Please visit our Cytokine & Chemokine Detection ELISA Kits page for a complete list of the ELISA kits we offer and suggested animal models for your research needs.
In recent years the FDA has approved cancer therapies relying on immune checkpoint inhibitors, antibodies that specifically target immunoregulatory receptors such as cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) and programmed cell death protein 1 (anti-PD-1). These antibodies induce T-cell activation by preventing binding between receptors and their ligands. This new class of cancer therapeutics has been successful in the treatment/management of aggressive cancers, doubling the median survival rate (1). In aggressive cancers like melanoma, cancerous cells generate a tumor microenvironment (TME) that promotes tumor growth and proliferation, leading to a destructive cancer type. Within the microenvironment, naive T-cells differentiate into T-regulatory (Treg) cells which are actively accumulated into the tumor. Treg cells are highly immune suppressive and assist in the maintenance of immune homeostasis by protecting from developing autoimmune diseases and allergies, yet in the malignant TME they promote tumor progression by suppressing antitumor immunity. Treg cells can suppress antitumor T-cells by several mechanisms, including the expression of CTLA-4, while tumor cells can also suppress antitumor T-cell activation through expression of the ligands PD-L1 and B7-1 (CD 80) (1,2). T-cells are partially regulated by IL-2 and IFN-γ release, however when T-cells are suppressed by CTLA-4 and PD-1 mechanisms they lose proliferative activities, cytotoxic activities, and production of cytokines TNF-α, IL-2, IL-6, and CXCL1 (3).
Within the TME there are many different chemokines responsible for cell recruitment, tumor growth and progression. The melanoma environment is associated with CXCL1, CXCL2, CXCL3, CXCL8, CCL1, CCL2, CCL5 and CCL22 (4,5). The role of CCL22 in immune-homeostasis is well described and several types of immune cells, such as macrophages, dendritic cells (DCs), B cells, and T cells, secrete CCL22 upon activation. CCL22 is a known chemoattractant of Treg cells and the chemokine is increased in the melanoma affected skin. Recent studies have used CCL22 vaccination as a strategy to differ Treg from the melanoma site, limiting excessive Treg accumulation and melanoma growth (5,6).
Chondrex, Inc. provides Mouse Anti-Mouse CTLA4 and PD-L1 monoclonal antibodies which can prevent the binding of their respective receptor and ligand. These antibodies are applicable to many types of mouse cancer models and are especially useful for long-term animal studies such as carcinoma models (7). Chondrex, Inc. has tested their cancer anti-mouse antibodies and our studies have shown decrease in tumor size with the melanoma model. If you would like more information about our melanoma model results, please contact us.