Immune cells work to fight infection and other diseases. Different subsets work together to elicit a healthy immune response; however, infections and disease can dysregulate cells and prevent effective immunity. Interestingly, cancer can use immune cells to its advantage.
Cancer employs various mechanisms to alter the immune system. Once established, tumor cells secrete proteins and molecules to generate a favorable environment. In this case, the tumor microenvironment (TME) becomes hypoxic due to a lack of oxygen with increased blood vessel growth to bring nutrients to the tumor and altered cell types that promote tumor progression. Specifically, tumor-secreted molecules polarize healthy immune cells, which allow cancer cells to proliferate and travel to distal tissues of the body.
T cells are specific immune cells responsible for identifying and targeting pathogens. Receptors on T cells recognize proteins on the surface of infected cells, which stimulate an immune response that eliminates the disease. These cells are critical for effective health and many immunotherapies aim to amplify or enhance T cell function. In the context of cancer, these T cells lose their function and, in some cases, promote tumor growth by inhibiting other immune cells. Unfortunately, treatment efficacy is limited to specific subsets of patients due to tumor type and stage of disease. Scientists are currently working to understand more about T cell biology and enhance immunotherapy.
A recent article in Cell, by Dr. Carmit Levy and others, demonstrated that melanoma cancer cells can ‘paralyze’ immune T cells. The underlying mechanism prevents effective T cell function toward melanoma and may serve as a targetable approach in cancer treatment. This discovery is a collaborative effort between multiple institutions across Israel and in Europe. Levy is an Associate Professor in the Department of Human Genetics & Biochemistry and a Sackler Faculty of Medicine at the Tel Aviv University in Israel. Her work focuses on understanding how genetic material can promote carcinogenic mutation in skin cells that develop into melanoma. Levy and her team hope to develop novel therapeutic approaches for the treatment of skin cancer.
Extracellular vesicles (EVs) are tiny, secreted bubbles that contain biological material derived from the cell. It is through this form of material transfer that melanoma can ‘paralyze’ immune cells. Researchers focused on stage II melanoma since it is known that the cancer commonly progresses to the inner dermis layer and metastasizes to the blood and lymphatic system. Previous work by Levy report that at this stage melanoma cells secrete EVs, known as melanosomes, that drive metastasis to the blood by forming a specialized compartment or niche that create an environment favorable to the cancer.
Ligands on EV membranes were found to bind to T cells and inactivate function. In some cases, EVs even kill cells to avoid being targeted. Interestingly, it appeared that cancer cells were purposely secreting these EVs as a protective mechanism against immune cells. This is a major discovery in cancer research. Although more work needs to be done, this work provides insight into how scientists can strengthen immune cell response and avoid EVs secreted from the tumor. Overall, this research has the potential to enhance current immunotherapy and has far-reaching therapeutic implications.
