Artificial molecules boost cancer therapy

Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. Immunotherapies are breakthrough treatments that stimulate the patient's immune cells to attack the tumor through the recognition of tumor antigens.

Dendritic cells are specialized immune cells whose role is to capture antigens from foreign bodies and present them to the immune system's killer T cells, which will then attack and destroy the invaders. For the vaccine, dendritic cells are taken out of the patient, "force-fed" with tumor antigens, and finally re-injected back into the patient. The idea is to facilitate the ability of the dendritic cells to prime killer T cells against the tumor, which is notoriously skilled in concealing itself from the patient's immune system.

Dendritic cell vaccines have achieved some clinical success but not without several limitations. For example, the tumor antigens used to "feed" the dendritic cells are generally not taken from the patient's tumor but from lab-grown cancer cells that are only partially similar to those of the patient. This can limit the power of the vaccine because its tumor antigens may differ from those of the patient's tumor, meaning that the killer T cells would not be properly activated to recognize and attack the tumor.

A group of researchers led by Michele De Palma at EPFL have now created artificial receptors called EVIR (extracellular vesicle-internalizing receptors), which enable the dendritic cells in the vaccine to selectively and efficiently capture antigens from the actual patient's tumor. This is achieved by inserting the EVIR into the dendritic cell, where it recognizes a protein on small vesicles called exosomes.

Exosomes are profusely released by the tumor and contain a variety of tumor antigens. They are also increasingly implicated in the promotion of metastasis and other processes that may facilitate the growth and spreading of cancer. By capturing exosomes coming from tumors, the EVIR helps the dendritic cells to precisely acquire tumor antigens from the cancer cells. The dendritic cells then present these antigens more efficiently to killer T cells, thus amplifying the patient's immune response against their tumor.

Imaging techniques also revealed that EVIRs promote the direct transfer of tumor antigens from the exosome surface to the outer membrane of the dendritic cell. This is a fascinating and unconventional route for antigen presentation to T cells,  which does not require complex and rate-limiting molecular interactions inside the dendritic cell.

The EVIR technology can intercept a natural phenomenon - the release of exosomes from tumors - to the patient's benefit, it exploits pro-tumoral exosomes as selective nanocarriers of tumor antigens, making them available to the immune system for cancer recognition and rejection. Although the new technology has the potential to increase the efficacy and specificity of dendritic cell vaccines, further pre-clinical work is required before it can be translated into a cancer treatment.
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Cancer cells suppress the immune system

Human immune systems prevents different diseases including cancer, for cancer to spread and multiply, they must find a way to avoid the body's immune system.

Degenerated cells in the body cause an inflammatory reaction and influence other blood cells to the extent that the immune system is suppressed.

Tumor cells influence their environment in order to avoid an immune response and to facilitate their growth. Solid tumors manipulate macrophages of the immune system.

The relationship between leukemia cells and monocytes becomes a catalyst for cancer development. Programmed death-ligand 1PD-L1 also known as cluster receptor occurs more frequently on the surface of these nourishing cells, and suppresses the immune response for cancer to grow.

The immune response is suppressed so much that the cancer cells can multiply without any hindrance. The monocytes send out semiochemicals, which belong to the inflammation response of the immune system and support the growth and multiplication of the cancer cells.

Scientists treated monocytes and macrophages of humans and mice with suspect exosomes, as well as purified Y RNA from those exosomes, in a culture dish. In both cases, the cells changed similarly to how they would in chronic lymphatic leukemia CLL patients.

They carry more PD-L1 receptors to their surface and emit semiochemicals that accelerate the immune response and create favorable growth conditions for leukemia cells.

Adding Toll-like receptors TLR inhibitors such as Chloroquin, a medication used for malaria and rheumatic inflammation can inhibit YRNA.

CLL cells was able to suppress the reproduction of cancer cells markedly.
This makes Chloroquin a good substance for a combination therapy along with other agents for cancer treatment.
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Brain cells control aging

Scientists have discovered that stem cells in the brain's hypothalamus control how fast aging occurs in the body. This discovery could lead to new method of preventing diseases and increasing lifespan.

The hypothalamus regulates growth, development, reproduction, metabolism and aging. The number of hypothalamic neural stem cells naturally declines and this accelerates aging.
Replenishing stem cells can slow down the process of aging but the loss are not irreversible.

Researchers disrupted the hypothalamic stem cells in middle-aged mice and discovered that disruption accelerated aging. They injected hypothalamic stem cells into the brains of middle-aged mice whose stem cells had been destroyed as well as into the brains of normal old mice.

The treatment showed different measures of aging in both groups. Hypothalamic stem cells exert their anti-aging effects by releasing microRNAs (miRNAs).

The researchers extracted miRNA-containing exosomes from hypothalamic stem cells and injected them into the cerebrospinal fluid of middle-aged mice whose hypothalamic stem cells had been destroyed and normal middle-aged mice.

This treatment slowed aging in both groups of animals as measured by tissue analysis and behavioral testing that involved assessing changes in the animals' muscle endurance, coordination, social behavior and cognitive ability.
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