Fat in obese people "clogs" cancer-fighting cells

Summary: Cancer, immunity and fatty tissue

Research published in the journal Nature (12.Nov.2018) indicates that the fat in adipose tissue of obese subjects harms tumor killer cells, it clogs their metabolism, and this does not allow them to find and destroy cancer cells.

Fat, obesity, and cancer

The link between cancer and obesity is well known, and almost half de cases of certain types of cancer are due to this reason (including kidney, breast, liver, and pancreatic cancers).

There are many possible mechanisms by which fatty tissue can cause cancer such as excessive production of hormones, insulin, and adipokines by adipose tissue.

Adipokines are hormones and cytokines that depending on the situation can provoke or reduce inflammation.

The body keeps tumors under control by detecting the rogue cells at an early stage of development. It uses immune cells to seek tumors and kill them (natural killer cells or NK and CD+ T cells).

A paper published in Nature (Michelet et al., 2018) (1) reports that fatty tissue "gums up" this immune reaction and impairs the cancer-killing effect of these immune cells.

The NK cells are the body's first line of defense against cancer cells. They detect tumor cells and kill them by secreting toxic products such as perforin and granzymes.

In obese subjects, the fatty environment with abundant lipid accumulation interferes with the NK cells' metabolism.

In other words, the fat in obese people's tissue halts the energy production inside NK cells, and this blocks their anti-tumoral activity.

The authors describe this negative effect as follows: "obesity induces robust ... lipid accumulation in NK cells, causing complete 'paralysis' of their cellular metabolism and trafficking ... This prevented trafficking of the cytotoxic machinery to the NK cell-tumor synapse."

The outcome is that the cytotoxic products (which means the cell-killing chemicals produced by the NK cells) can't reach the tumor because fat accumulates inside the NK cells.

References and Further Reading

(1) Michelet X, et al., (2018). Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol. 2018 Nov 12. DOI: 10.1038/s41590-018-0251-7