Cancer Evades The Immune System

Tim Newman published an article that was fact checked by Honor Whiteman shedding light on how cancer evades the immune system. Researchers have long been puzzled on cancer’s ability to elude our body’s immune system. A recent study pinpointed one of cancer’s protective cloaks and investigates a way to remove it.

When abnormal cells called cancer cells have gone awry, they multiply unchecked and function incorrectly. Usually the cells that are faulty are either dead or dying and cleared away by the immune system. A type of white blood cells called macrophages, are mostly responsible for the consumption and destruction of foreign invaders and unpredictable cells.

The macrophages normally carry out the attacks with ruthless efficiency and some manage to evade their roaming gaze. So, how do cancer cells fly under the radar of the immune system? Dr. Irving Weissman, director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, published research in 2009 that goes toward answering this question. There is a “don’t eat me” signal on cancer cells that they have identified.

Weissman demonstrated that aggressive cancer cells express higher levels of CD47 on their cell surface. CD7 is a transmembrane protein that binds to a protein called SIRPalpha on the surface of macrophages and reduces their ability to attack and kill the cancer cells.

Animals have shown through studies that treatment with an anti-CD47 antibody can significantly increase macrophages’ ability to kill cancer cells. In some mouse studies, the treatment led to a cure and clinical trials are being conducted to gauge if this approach will be as successful in humans as mice studies.

Another research paper was published by Weissman’s team that uncovers another “don’t eat me” signal. A molecule in focus is a cell surface protein called major histocompatibility complex class 1 (MHC class1).

Once our immune system responds to a specific pathogen, it can mount a swift and specific response if it meets the same intruder again. An important part of this wing of the immune system is MHC class 1. These are found on the surfaces of most of our cells and taking portions of internal cellular proteins to display them on the cell’s surface, provides a snapshot of the cell’s health. The T cells destroy the abnormal cell’s protein flags. The interaction between MHC class 1 and T cells is well described, but it is not fully understood how macrophages are involved.

In a current study, a protein LILRB1 that is on the surface of macrophages binds to a part of MHC class 1 on the surface of cancer cells. Once bound it will prevent the macrophage from consuming and killing the cell. Inhibiting the CD47-mediated pathway and the LILRB1 pathway, it interferes with both “don’t eat me” signals and tumor growth was significantly slowed in mice. Nature Immunology published the results.

When simultaneously blocking both of these pathways, it resulted in the infiltration of the tumor with many types of immune cells and significantly promoted tumor clearance, resulting in smaller tumors overall. Immunotherapy for cancer is rapidly developing, but it is a complex one as different cancers have different immunological fingerprints. Some cancer cells reduce the levels of MHC class 1 on their cell surfaces, helping them to evade T cells.

Cancers might not always respond well to traditional therapies designed to enhance T cell activity, but these cancers might be more vulnerable to an anti-CD47 approach. Cancers with plentiful MHC class 1 might be less affected by anti-CD47 treatment. Understanding how these pathways might be overturned is a difficult but critical endeavor and marks another step toward teaching our immune system how to slow cancer’s onward march.