A collaborative team of scientists from Denmark, France, the UK, and the US recognized the potential to target CD163 macrophages for a novel approach to cancer immunotherapy.
Macrophages are one of many types of immune system cells of the body, and they function to phagocytize and digest invading substances including bacteria and other microorganisms; they also digest cellular debris and cancer cells. However, there are a subset of macrophages (CD163 macrophages) that actually supports tumor survival and impedes T-cell attack of tumors. Expression of CD163 by these macrophages is associated with a poorer prognosis for a number of human cancers, such as malignant melanoma.
Current approaches involve enhancing direct attacks on tumor cells by the immune system. An example is the use of checkpoint inhibitors that block proteins that stop immune system attacking of cancer cells. A novel approach would involve manipulating or depleting CD163 cells to remove the protections they provide for tumor cells.
To study the role of CD163 macrophages in cancer cell survival, the researchers conducted studies to characterize tumor-associated macrophages (TAMs) in a melanoma mouse model resistant to anti–PD-1 (checkpoint inhibition) immunotherapy. Then, studies were designed to target those TAMs that express CD163. They used antibody-conjugated lipid nanoparticles to target and deplete the CD163 TAMs and found that this targeting led to tumor regression in the mouse model.
Looking more deeply at the effects of CD163 TAM depletion, the researchers found that there was a 6-fold increase in the tumor-infiltrating leukocyte compartment. They saw a very significant infiltration of cytotoxic T cells and mobilization of inflammatory monocytes, further contributing to tumor regression. This information can shed light on the limited efficacy of currently studied cancer immunotherapeutic approaches. Also, the development of immunotherapy strategies targeting CD163 TAMs can enhance the availability of anti-cancer treatments, particularly for patients who do not respond well to current approaches.
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Researchers discover a new form of immunotherapy. (2019). Medicalxpress.com. Retrieved 6 November 2019, from https://medicalxpress.com/news/2019-08-immunotherapy.html