A new pathway to shrink cancerous tumours through body’s immune cells

21 Apr 2022
A new pathway to shrink cancerous tumours through body’s immune cells

Cancer researchers at the Case Western Reserve University School of Medicine say they have successfully suppressed the growth of some solid tumours in research models by manipulating immune cells known as a macrophages. 

The researchers say this discovery is significant as many solid tumour cancers like lung cancer are difficult to treat.

According to the National Cancer Institute, breast, lung, prostate and colorectal cancers—which are all solid tumour cancers­–­­­account for almost half of all new cancer cases in the United States.

In this new research, the scientists discovered that altering the macrophage metabolism—and in doing so influence their relationship with T cells—suppressed the tumour’s growth.

The result was a significant reduction in overall tumour size in some mouse models.

“The race to find a cure for cancer never stops,” said Stanley Huang, an assistant professor of immunology in the Department of Pathology at the School of Medicine, who led the research. “Our research creates a pathway to a [potential] new form of cancer treatment for those with solid tumour cancers.”

The study appeared recently in the journal, Nature Immunology.

Generally, the body’s immune response to disease involves mobilising white blood cells that attack invaders like germs and bacteria.

Macrophages are specialised white blood cells that consume invading cells to destroy pathogens.

They are considered the “frontline soldiers” of the body’s immune system and can activate T cells, which are another type of white blood cell.

Yet, despite their typically protective role, macrophages can be co-opted by tumour cells to encourage tumour growth.

As tumours grow and macrophages interact with the tumour cells, they create a response protein, which the study linked to tumour growth.

Huang said the team believed it was possible to target macrophages and that protein—known to scientists by its shorthand, PERK (“protein kinase R” (PKR)-like endoplasmic reticulum kinase) to block tumour growth.

“Knocking out PERK suppresses downstream metabolic signalling in tumour macrophages, resulting in more T cells to fight the cancer cells,” said Huang.

The study’s findings suggest that the PERK protein is involved in several key pathways of metabolism in macrophages—and when the gene is removed, macrophages can no longer promote tumour growth; meaning tumours become smaller.

Follow-up experiments further revealed that combination treatment of a PERK inhibitor drug with an inhibitor called “anti-PD-1” could significantly reduce tumour growth.

Next, the researchers hope to identify a clinical drug that will act as an inhibitor for the PERK protein.

“There are several strategies to enhance anti-tumour immunity like targeting or editing cell metabolism,” Huang said. “We can target genes and their pathways to enhance immune function and work toward future therapeutic treatment options.”

Source: Case Western Reserve University