Cancer is a disease in which mutated cells grow rapidly and uncontrollably. Unfortunately, these cells resist the body’s immune response and override immune response mechanisms to progress. Cancer is characterized by many different features, including chronic inflammation, which polarizes healthy immune cells to promote tumor growth. Tumor cells secrete specific proteins that change the function of immune cells. In addition, these same proteins can help tumors become undetectable to the host immune system. Different cancer immunotherapies work to overcome immune cell polarization elicited by the tumor. Immunotherapies work to reactivate and enhance the tumor immune response to better recognize and target mutated cells.
One example of immunotherapy includes immune checkpoint inhibitors (ICI). This therapy is designed to activate immune cells that were inactive due to tumor cell secreted proteins as well as surface markers on tumors that prevent immune cell activation. Specifically, the immune cells the therapy targets are known as cytotoxic T cells, which are responsible for targeting and eliminating foreign invaders and cancer cells from the body. T cells are part of the second wave of immune defense within the adaptive immune response. Immune checkpoint inhibitors block a surface marker on T cells, known as programmed cell death protein 1 (PD-1). This PD-1 blockade on T cells stimulates activation and results in tumor cell death. This therapy has been demonstrated to successfully treat various cancers but is much more effective even in combination with standard-of-care treatment, including chemotherapy. However, side effects of ICI therapy include susceptibility to common infections and scientists are working to understand more about how these effects can be averted.
A recent study in Immunity, by Dr. Stuart G. Tangye and others, demonstrated that antibody production is reduced after ICI therapy is given to cancer patients. Tangye is a professor of Medicine and Health in the School of Clinical Medicine at the University of New South Wales Syndey (UNSW Sydney). He is also a member of the Garvan Institute of Medical Research where he leads a lab focused on immunology and immunodeficiency. Previously, it was recorded that roughly 20% of cancer patients that were treated with ICI experienced common infections.
The team discovered that ICIs dysregulate B cells, which are specialized immune cells designed to generate antibodies against pathogens entering the body. With the lack of B cells functioning, antibody production is reduced and patients become more susceptible to disease. Tangye and others discovered that impaired or absent PD-1 (caused by ICI) resulted in reduced quality of antibodies that are generated for immune cell memory. This memory immune response recognizes previous invading pathogens and helps the body rapidly response to infection. However, antibody dysregulation prevents patients from responding immediately to external diseases.
The work conducted by Tangye, and others better informs physicians of the off-target effects of ICI therapy. As a result, physicians can monitor B cell function and possibly treat patients with an antibody therapy to counter the effects of ICI. This work is groundbreaking due to the uncovered mechanism behind infection susceptibility after ICI treatment. Scientists can now refine ICI therapy to not only maintain anti-cancer effects, but also preserve immune system function to accurately fight infections.
Study, Immunity, Stuart G. Tangye, UNSW Sydney, Garvan Institute of Medical Research
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