25 December 2017

T-helpers in the treatment of aggressive tumors

Adoptive cell transfer (APC) is one of the options for cancer immunotherapy. To implement it, a doctor takes T-lymphocytes from a blood sample of an oncological patient, then modifies them in the laboratory to increase antitumor activity. After that, they are injected back into the patient's blood so that they find and destroy cancer cells.

APC is currently considered the most effective treatment for melanoma and many types of cancer. Unfortunately, it is poorly effective against solid tumors, for example, pancreatic cancer.

There are hundreds of types of T-lymphocytes in the body, but not all of them effectively fight cancer, especially when it comes to extremely aggressive tumors. For successful APC, T-lymphocytes must be able to find the tumor, get to it and survive for a long time in harsh enough conditions to destroy cancer cells.

A group of researchers from the Medical University of South Carolina set out to increase the effectiveness of APC therapy. They were able to detect the CD26 protein, the presence of which on the surface of the T-lymphocyte indicates a high antitumor potential of the cell.

The fact is that most of the researchers in this direction are devoted to the CD8 type of T-lymphocytes (T-killers). This time, CD4 cells were under close attention.

CD4, they are also T-helpers, as previously thought, cannot destroy cancer cells, but only help other immune cells to do so. And now a new study proves that their abilities have been underestimated.

The researchers focused their attention on the type of T-helper cells (th17-lymphocytes), which are very effective in fighting solid tumors. CD26 protein, characteristic of th17 lymphocytes, helped to isolate these cells from the lymphocyte population.

CD26 protein is present on the surface of all T-helper cells, but its quantity is different: most of it is on the surface of th17 lymphocytes.


T-helper cells with a high content of CD26 protein on the cell surface (marked in red).

Investigating the properties of T-helpers obtained from the blood of patients, the authors found their amazing ability to survive for a long time in adverse conditions and effectively destroy solid tumor cells. The presence of a large amount of CD26 protein on the surface of the studied cells gave them characteristics that other T-lymphocytes lacked. Firstly, they could resist apoptosis and survive in a hostile environment. Secondly, T-helpers had the properties of stem cells that allowed them to divide and grow after being injected into the patient's blood.

The beauty of APC therapy is that it is "alive": after the T-helpers have fulfilled their function and destroyed cancer cells, they continue to live in the patient's body. If suddenly the tumor starts to grow again, these cells will attack the cancer cells again. Theoretically, T-lymphocytes are able to live in the human body for more than 20 years.

Thus, the high content of CD26 protein on the surface of T-helper cells can be considered as a marker for identifying cells with the greatest potential for cancer immunotherapy. In addition, the researchers were able to prove in vitro the effectiveness of T-helpers with CD26 protein in the fight against aggressive solid tumors. As the researchers suggest, the amount of CD26 protein directly correlates with the therapeutic effect.

In animal models, the treatment of meloma, mesothelioma and pancreatic cancer with T-helpers was studied. The effectiveness of treatment directly depended on the number of T-lymphocytes with CD26 protein that penetrated into the tumor tissue. Melanoma was cured in 50% of cases, mesothelioma – in 95%. There was no complete cure of pancreatic cancer, but the tumor decreased by two-thirds in response to treatment, and survival rates improved. In combination therapy with CD26 protein, the cells are likely to be effective.

The use of cells with CD26 protein can be a promising direction in immunotherapy of oncological diseases both as monotherapy and as part of combination therapy in combination with receptor modulators, vaccines and cytokines. In addition, T-helpers with a high content of CD26 protein can be used in the treatment of autoimmune and infectious diseases.

Article by Stefanie R. Bailey et al. Human CD26high T cells elicit tumor immunity against multiple malignancies via enhanced migration and persistence is published in the journal Nature Communications.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of MUSC: Overlooked immune cells hold breakthrough for treating aggressive cancers.

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