A New Mechanism by Which Cancer Cells Inhibit Anti-tumor Immune Response Being Released by Journal of Nature
Tumor cells are not just a group of cells that are out of control, they actively participate in the struggle with the immune system for their own survival which is featured of the capability to evade detection from the immune system.
- Joplin, MO (1888PressRelease) January 31, 2019 - In a new study, researchers from the University of Pennsylvania found that cancer cells release biological "unmanned aerial vehicles" to help with the fight - small vesicles that carry the PD-L1 protein called exosomes circulating in the blood which causes T cells to be exhausted before reaching the tumor and fighting. Although the study focused on metastatic melanoma, researchers found that breast cancer and lung cancer also release exosomes carrying PD-L1. The related result is published in the Journal of Nature.
The study demonstrated how cancer can adopt a systematic approach to suppressing the immune system in a way that subverts existing ideas. In addition, it provides a new way to predict which cancer patients will respond to anti-PD1 therapy by destroying immunosuppression against tumors and provide a way to track the effects of such treatments.
One of the most successful innovations in cancer treatment is the application of immunological checkpoint inhibitors, which are designed to prevent cancer cells from suppressing the immune system and allowing tumors to thrive and spread. One of the main targets of such drugs is PD-1, that is, a protein located on the surface of T cells. On the surface of tumor cells, they express a corresponding molecule called PD-L1, which interacts with the PD-1 protein on the surface of T cells, effectively shutting down the anti-cancer response of T cells. Blocking this interaction with an immunological checkpoint inhibitor reactivates T cells, allowing them to release the ability to kill cancer cells in the tumor.
Although tumor cells are known to carry PD-L1 on their surface, however, in this study, these researchers found that exosomes from human melanoma cells also carry PD-L1 on their surface. The exosomes PD-L1 bind directly to T cells and inhibit the function of these T cells, the identification of exocytic PD-L1 secreted by tumor cells provides a major update to the immune checkpoint mechanism and provides new insights into tumor immune evasion.
As a single tumor cell is capable of secreting many copies of the exosomes, the interaction between the exosomes carrying the PD-L1 and the T cells provides a method to systemically and efficiently inhibit the anti-tumor immune response systemically, which may explain the reason why the immune system of cancer patients may be weakened. Based on the circulation of exosomes in the blood, they provide a viable method for monitoring cancer/T cell struggles through blood tests compared to traditional invasive tumor biopsies. After the acute treatment phase, these researchers envisioned a test method that monitors how the drug controls cancer cells.
Oncologists may be able to predict the tumor burden of patients and correlate it with treatment outcomes by measuring pre-treatment PD-L1 levels. In addition, blood tests may measure the effectiveness of treatment, such as PD-L1 levels in exosomes may indicate the level of activation of T cells by immune checkpoint inhibitors.
Guo, one of the researchers said that, ‘In the future, we will start to treat cancer as a chronic disease, just like diabetes. Diabetics utilize blood glucose meters to measure blood glucose levels, monitoring PD-L1 and other biomarkers on circulating exosomes may be a way for clinicians and cancer patients to pay close attention to cancer treatment. This will be another step towards achieving the goal of precision medicine and personalized medicine.’
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