Anti Tumoral Immune Response Protin : Discovery
Researchers at the German Cancer Research Center (DKFZ) have made a significant discovery in the battle against cancer. They’ve pinpointed a special kind of protein on the surface of cancer cells. This protein plays a crucial role in fortifying a key element responsible for activating T-cells, which are vital in our body’s defense against tumors. This breakthrough holds the promise of bolstering our immune system’s ability to combat cancer effectively.
In recent years, immune checkpoint inhibitors, like the anti-PD-L1 antibody nivolumab, have emerged as highly potent treatments for various types of cancer. Regrettably, there are instances where a deficiency in the activating signals for T cells can result in an unsuccessful outcome for immunotherapy. This means that even with the advancements in this field, there are still challenges to overcome in ensuring the effectiveness of these treatments.
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A pivotal signal for activating T cells hinges on the co-stimulatory protein CD58. When it binds with its receptor on an immune cell, it triggers an inflammatory response, resulting in a more robust defense against tumors. In a report featured in Cancer Cell, scientists have unveiled a membrane protein present on cancer cells, identified as CMTM6. This protein has the remarkable ability to engage with and positively influence CD58, potentially amplifying the anti-tumoral immune response.
“It is intriguing to observe that many cancer cells inherently express CD58, a molecule that essentially contradicts their own survival when they come under immune attack. We therefore wanted to understand what controls the expression of CD58,” explained Chong Sun, PhD, an immunologist at the DKFZ and co-author of the study.
According to the researchers, CMTM6 surprisingly also interacts with PD-L1—a T cell blocking receptor expressed on cancer cells targeted by most checkpoint inhibitor treatments. In the study, CMTM6 protected PD-L1 from degradation while simultaneously stabilizing CD58. This dual action could potentially have significant implications for enhancing the effectiveness of checkpoint inhibitor therapies.
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Intriguingly, both CD58 and PD-L1, key players in our immune system with contrasting roles, are regulated by CMTM6. What adds to the intrigue is that when examining samples from patients who underwent ICI therapies, it seems that CD58 could potentially play a prominent role in influencing the response, in most instances. This insight comes from the study’s first author, Beiping Miao, PhD, a postdoctoral researcher at DKFZ.
In order to delve deeper into CD58’s role in fighting tumors, the researchers conducted experiments using a cell culture model with T-cell receptors. Their findings demonstrated that when CMTM6 was absent, it hindered T cell activation, underscoring the crucial role of this protein in our body’s immune response.
Through experiments involving mice carrying transplanted human leukemia cells, the team showcased that the absence of CMTM6 proteins shielded cancer cells from CAR-T therapy. Furthermore, in human cancer cells obtained from tumor biopsies, the researchers noted widespread presence of both CMTM6 and CD58 proteins. Interestingly, higher levels of these proteins were linked to more favorable responses to immunotherapy.
In a press statement, it was concluded by Sun, “Our findings highlight the importance of CMTM6 and CD58 expression in cancer cells during an immune response against tumors. Our next step is to explore the possibility of adjusting their expression in laboratory experiments. Our goal is thereby finding a way to improve cancer immunotherapies.”
Conclusion
Thus , the research conducted at the German Cancer Research Center (DKFZ) unveils critical insights into the interplay of proteins in the immune response against cancer. The discovery of CMTM6’s dual role in regulating CD58 and PD-L1 marks a significant advancement in understanding tumor immunology. Notably, experiments with T-cell receptor treatment models and human leukemia-bearing mice underscore CMTM6’s pivotal role in T-cell activation and susceptibility to CAR-T therapy. The widespread presence of CMTM6 and CD58 in human cancer cells further emphasizes their significance. The potential to manipulate their expression offers a promising avenue for enhancing cancer immunotherapies, presenting a hopeful prospect for future treatments.
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