CXCL10: a promising marker for immunotherapy response in metastatic melanoma
Immunotherapy has emerged as a major new type of treatment for cancer. This form of therapy is a way of harnessing a patient’s own immune system to recognize and destroy tumor cells. One of the most widely utilized type of immunotherapy drug targets an immune inhibitory pathway called PD-1. Drugs blocking PD-1 have been FDA approved for 15 distinct cancer entities. Despite this important success, many patients do not respond to anti-PD-1 therapy. The laboratory of Thomas Gajewski, MD, PhD, has been focusing on identifying the mechanisms involved when anti-PD-1 works, in order to develop new therapies that can turn non-responders into responders.
Gajewski is a clinician-scientist and the AbbVie Foundation Professor of Cancer Immunotherapy. His lab studies how a type of immune cells, called T cells, can fight melanoma and other cancers. A major factor driving the attraction of T cells into tumor sites was found to be a chemokine called CXCL10. This chemokine binds a receptor on activated T cells called CXCR3, which promotes directional trafficking of T cells into the tumor. In a recent study published in the Journal of Immunotherapy of Cancer, an MD fellow in the lab, Robin Reschke said, “One major goal is understanding how T cells infiltrate tumors. If we can confirm this mechanism, then perhaps we can develop new therapies that induce T-cell recruitment to cancer sites to expand immunotherapy effectiveness. Since checkpoint blockade immunotherapy works best in a T cell-inflamed tumor microenvironment, I think there will be a huge opportunity to make use of this crosstalk between the tumor microenvironment and T cells, orchestrated via chemokines, to markedly improve the efficacy of anti-PD-1”.
An additional goal of this study was to identify the cellular sources of CXCL10 by capitalizing on a commercialized technology known as RNAscope. This technology allows someone to see by fluorescence where (i.e., in which cell types) specific RNA molecules are produced. They found that the mRNA needed for making CXCL10 protein was most abundant in immune cells (mostly dendritic cells and macrophages) but also in the tumor cells (see image).
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