Home Scientific Research Scientists Found An Immune Cell Helps Kill Bladder Cancer Cells

Scientists Found An Immune Cell Helps Kill Bladder Cancer Cells

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Scientists Found An Immune Cell Helps Kill Bladder Cancer Cells
Scientists Found An Immune Cell Helps Kill Bladder Cancer Cells

Mount Sinai researchers have made two significant findings about the process by which bladder cancer cells evade immune system responses. The study, which was published in September’s issue of Cancer Cell, may result in a new therapeutic approach for patients with these kinds of cancers.

Most people with advanced bladder cancer don’t have a good chance of getting better. The Food and Drug Administration has licensed a number of immune checkpoint inhibitors for bladder cancer, but only approximately 20% of patients experience sustained favorable responses.

When people develop cancer, a type of immune cell known as a “natural killer cell” attempts to eliminate the tumor cells. But most of the time, the tumor cells can stop the natural killer cells from killing them. The Mount Sinai researchers revealed that they had discovered a subgroup of CD8 T cells that adapts to tumor evasion tactics by appropriating innate-like qualities usually attributed to natural killer cells, providing a method to lessen the tumor cells’ capacity to fight them off.

The researchers demonstrated that they could drive CD8+ T cells to produce a protein known as NKG2A on their surface, allowing them to behave more like natural killer cells and producing extra killer cells. This study demonstrated a relationship between NKG2A and increased survival as well as responsiveness to the immunotherapy drug PD-L1 checkpoint blockage.

The second finding is about how PD-L1 checkpoint blockade therapy can make cancer cells stronger. Because HLA-E attaches to the NKG2A molecule and impairs the T cells’ ability to fight, the researchers noted that cancers can continue to express the HLA-E protein on their surface. This protein allows them to resist T cells. These patients’ tumors may respond well to immunotherapy that particularly targets the HLA-E/NKG2A axis, according to the findings.

The results, according to lead and co-corresponding author Amir Horowitz, “suggest that antibodies that block both NKG2A and PD-L1 could be a more effective treatment strategy for patients whose bladder cancer tumors have both high levels of HLA-E and NKG2A-positive CD8+ T cells.” 

The results, according to lead and co-corresponding author Amir Horowitz, “suggest that antibodies that block both NKG2A and PD-L1 could be a more effective treatment strategy for patients whose bladder cancer tumors have both high levels of HLA-E and NKG2A-positive CD8+ T cells.” 

These results offer a foundation for future clinical trials that include various immunotherapies and a medication that inhibits NKG2A in these malignancies.

“Immune checkpoint blockade,” adds Co-corresponding author Nina Bhardwaj, “is a leading type of cancer immunotherapy that targets the PD1-PDL1 pathway in order to re-engage ‘exhausted’ CD8+ T cells in the fight against tumors.” 

In this study, they demonstrated that responses to PD-L1 blockage in bladder cancer patients are controlled by another immune checkpoint axis, NKG2A-HLA-E, that has recently been discovered in other malignancies.

In order to acquire live immune cells and analyze their functioning, the researchers examined tumors and blood from bladder cancer patients at various stages of the disease. All specimens were studied shortly after surgical removal from patients. The Cancer Genome Atlas (TCGA) and the ImVigor210 trial of the anti-PDL1 immunotherapy atezolumab were both used to access publicly available datasets for the study, which also combined a number of cutting-edge single-cell technologies.

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