Current treatments for cancer, such as radiotherapy and chemotherapy, use radiation or drugs to kill cancer cells and tumors in the body. However, some cancers resist these treatments and become hard to treat. 

An alternative treatment, called immunotherapy, trains immune cells to find and eliminate cancer cells in the body. Many immune cells have special proteins that suppress anti-cancer activities – immunotherapy targets these proteins to boost the immune cells’ ability to kill tumors.

One type of cancer immunotherapy boosts an immune cell called the dendritic cell. Dendritic cells find abnormal cells like cancer cells and break them down into pieces. The dendritic cells first go through internal changes to become mature, so they can stick cancer fragments onto their surfaces. The fragments of cancer cells, called antigens, are like labels that can be recognized by other immune cells. 

White blood cells in the immune system, called T cells, recognize the antigens that indicate cancer’s presence. The T cells then multiply into specific cancer-killing T cells. Mature dendritic cells also release molecules called cytokines that help fight the cancer cells.

Some proteins in the human body can prevent dendritic cells from maturing, thus limiting their anti-cancer activities. One of these proteins, called CTLA-4, is located on the surface of dendritic cells and controls the cells’ maturation. Scientists have previously shown dendritic cells made more antigen tags and released more cytokines when CTLA-4 was blocked.

Less mature dendritic cells also means less T cells are produced. Many current cancer drugs block CTLA-4, which increases dendritic cells’ abilities and T-cell production. Scientists have previously put normal dendritic cells into a solution of cancer antigens to activate their anti-tumor traits, but they have not yet tried combining these two therapies.

A group of scientists from Iran recently tested this combination, by blocking the CTLA-4 protein in dendritic cells, and then placing them into a cancer antigen solution. They predicted this strategy would improve dendritic cell activity and T cell production more than previously observed with the individual treatments.

The scientists obtained blood from healthy people. They collected T cells from the blood samples, and extracted stem-cell-like cells, called monocytes, that can be transformed into dendritic cells in the lab. They also collected a solution of colorectal cancer cells from the National Cell Bank of Iran. 

The scientists first created three groups of dendritic cells from the monocyte samples. Group A were untreated dendritic cells. Group B were dendritic cells where CTLA-4 was blocked. The scientists then combined Groups A and B with a solution of cancer pieces. As the tumor pieces were broken down, the dendritic cells matured and the debris stuck to the cells’ surfaces. Group C included dendritic cells that were untreated cells with no contact with the cancer solution. 

The scientists then combined each group of dendritic cell samples with T cells to study whether the combination of CLTA-4 blocking and cancer solution was more effective in increasing their cancer-fighting response. To determine how effective the treatment was, they tracked anti-cancer factors, including the number of anti-cancer T cells produced, and the amount of cytokines and other proteins that dendritic cells produced after contact with the cancer solution. 

The scientists observed the greatest increase in T cells and cytokines in Group B, where CTLA-4 was blocked. They interpreted these results as confirming that blocking CTLA-4 increases anti-cancer activities in combination with a cancer-antigen solution

The scientists concluded these results are promising for future cancer vaccine development. However, since this method was only tested in the lab, the next steps will be testing it in animals and eventually humans. They suggested further pre-clinical and clinical trials will be necessary to determine how safe and effective this method is in fighting tumors.

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