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Immunotherapy Effectiveness Tied to Particular Cell Activity

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Patients who do not respond to immunotherapy have reduced CD5 activity in their tumors, opening the door for more effective immunotherapy treatments.

New research indicates that how well cancer responds to immunotherapy may be related to the number and activity levels of CD5 dendritic cells in cancerous tumors.

If further research is conducted and a therapy is found to boost either the amount of CD5 cells or their activity levels within tumors, patients who had not previously responded to immunotherapies may see new benefits.

CD5 dendritic cells are glycoproteins, which many viruses use to enter cells, but also function within our immune system. Eynav Klechevsky, assistant professor of pathology and immunology and senior author on the study performed at Washington University School of Medicine in St. Louis, explained that patients who see reduced results from immunotherapies still have CD5 cells, but the tumors work to suppress their activity:

“They're not lacking (CD5 dendritic cells) entirely, they're just lacking (those cells) in the tumor. So, the tumor is doing something to actually manipulate the cells and suppress them. That's where we need to bring them to activity. In theory, (the cells are) there, they're hopefully helping us fight other infections, but the tumor probably has a way to manipulate them specifically.”

Immunotherapy works by boosting the activity of the immune system to attack cancerous cells and tumors more effectively, a process that is typically blocked by the tumor’s innate ability to suppress these functions wherever they grow. Tumors are also able to evade detection by manipulating the immune checkpoint system and ensuring killer T-cells do not attack them.

It is through this immunosuppression the tumor succeeds in growing and spreading beyond the site of initial disease, or metastasizing, leading to worse disease outcomes in patients.

Dendritic cells serve to regulate immune system function and are the main instigators of primary immune response, sending T-cells in to attack. When researchers analyzed data in the Cancer Genome Atlas, they saw patients with higher levels of CD5 dendritic cells also had better treatment outcomes.

Klechevsky said in the future researchers hope to develop a method of examining CD5 cell activity prior to immunotherapy treatment, allowing patients who would not benefit to avoid a needless line of therapy. There is also hope to develop new therapies that could stimulate CD5 activity in patients with very low activity, theoretically allowing all cancer patients to take advantage of immunotherapy treatments.

“We have some clues that we identified in this current study. But that's our goal is to see how we can expand them in patient, how we can activate them in patients or bring them to the right location. If they're not in the tumor, if they are not in lymphoid (tissue) in lymph nodes, where are they needed to activate the immune system? And how can we make them be there?”

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