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Identification of VISTA regulators in macrophages mediating cancer cell survival
While immune checkpoint therapies (ICT) are known to elicit T cell responses in the realm of oncology, their success remains limited to a small fraction of patients, and they are not universally effective against all types of cancer. It is indeed thus critical to understand the mechanisms driving adaptive resistance to these therapies and explore strategies to overcome them.The expression and immunoregulation of immune checkpoint molecule VISTA
The earliest described immune checkpoint is CTLA-4. The mouse gene for CTLA-4 was discovered in 1987, and the human gene was cloned the following year. It was not until the mid-1990s that CTLA-4 was shown to negatively regulate T-cell activation. The human CTLA-4 gene, located at 2q33, is constitutively expressed in regulatory T cells (Tregs) and can…
Reprogramming Immune Cells for enhanced Cancer Immunotherapy: Targets
Key keywords: cancer immune therapy, cell engineering, targets, strategies, immune cells. Introduction. Cancer incidence and mortality have been increasing since 2010, making cancer the leading cause of death and a major public health concern. Recent advances in immunotherapy have significantly increased survival and slowed progression of the tumor.
The findings highlight a potential path forward for treating late-stage tumors that have become resistant to current therapies, Abdrabou said.
“Most immunotherapy strategies right now are trying to remove roadblocks, for example, immune checkpoint blockade therapy,” Abdrabou said. “We’re not removing the roadblocks per se, but we’re trying to reprogram cells that the cancer managed to recruit back to being anti-tumor again.”
Moving forward, investigators will test the therapy in other cancer models and study the long-term effects, Abdrabou said.
“We’re really excited about the results, but at the same time we appreciate that cancer is a complex disease,” Abdrabou said. “We look at every cancer as its own disease and will continue to look into new technologies to dissect every cancer on its own.”
The study was supported by the National Institute of Health. Kelley is co-leader of the Cancer and physical Sciences Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Reference: Abdrabou AM, Ahmed SU, Fan MJ, et al.identification of VISTA regulators in macrophages mediating cancer cell survival. Sci Adv. 2024;10(48):eadq8122. doi: 10.1126/sciadv.adq8122
Identification of VISTA Regulators in Macrophages Mediating Cancer Cell Survival
While immune checkpoint therapies (ICT) are known to elicit T cell responses in teh realm of oncology, their success remains limited to a small fraction of patients, and they are not universally effective. This stops short of a extensive cure for cancer and has prompted researchers to delve deeper into the intricacies of the immune system’s role in combating cancer cells.
In a recent study published in *Science Advances*, a team led by Dr. Abdrabo, along with her colleagues Ahmed, Fan, and others, has identified placental Figure it out (VISTA) regulators within macrophages that considerably influence cancer cell survival. This groundbreaking study underscores the broader applications and complexities of macrophage behaviors within the tumor microenvironment.
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### Editor’s Interview with Dr. Kelley
#### Q: What prompted your research into VISTA regulators and their role in cancer cell survival?
A: Our interest in VISTA regulators came from the limited success rates of immune checkpoint therapies. We understand that cancer is a multifaceted disease that goes beyond simple T cell dynamics. The role of macrophages and other regulatory mechanisms within the tumor environment has become increasingly vital to investigate.
#### Q: How do VISTA regulators within macrophages impact cancer cell survival, and can you summarize your key findings?
A: Our study revealed that macrophage-mediated expression of VISTA within the tumor microenvironment plays a meaningful role in promoting cancer cell survival.,VISTA acts as a regulator that influences the interaction between macrophages and cancer cells.Our findings suggest that targeting VISTA could potentially enhance current oncology therapies by arresting mechanisms that support cancer cell survival.
#### Q: Can you discuss the implications of this study for immune checkpoint therapy and future cancer treatments?
A: certainly. This study highlights the importance of considering not just T cells but also macrophages and other regulatory mechanisms in the tumor microenvironment. By understanding these interactions, we can develop more tailored and effective therapies. This broadens the horizon for combining customary immune checkpoint therapies with novel treatments that target macrophages.
#### Q: What are the next steps after this discovery? Are there any clinical trials on the horizon?
A: We are very excited about these results but also recognise that more work needs to be done. We are looking into new technologies to further dissect the mechanisms within each type of cancer. Clinical trials focusing on targeting VISTA within tumor-associated macrophages are a possible next step. This area holds great promise,and we are continuing our research to maximize its potential in therapy.
#### Q: How do you think future research can build upon these findings?
A: Future research should aim to unveil the detailed mechanisms of how VISTA interacts with macrophages and other tumor microenvironment constituents. Developing animal models and exploring specific targeting strategies could help translate these findings into clinical settings. Collaboration between diffrent scientific disciplines will be key in this process.
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at the Lurie Comprehensive Cancer Centre of Northwestern University, researchers like Dr. Kelley are continuously pushing the boundaries of oncology,striving for more personalized and effective treatments.As we look to the future, their groundbreaking work holds the promise of turning the tide in the battle against cancer.
[Read the full study](https://doi.org/10.1126/sciadv.adq8122)
