Energizing the immune system to engulf cancer

[Wrichik Basu]

While @BillTre wrote about how scientists are trying to use the adenovirus in treating retinoblastoma, another team has published that the macrophages in the immune system can themselves engulf cancerous cells.

Macrophages have the power to engulf and destroy cancerous cells, but tumour cells release CD47 signals, which inactivate the macrophages against these cells. It is like a "don't eat me" command.

The team used this approach by activating macrophages with CpG, a toll-like receptor agonist that sends the first signal, and found that it rapidly induced shrinkage of tumors and prolonged survival of mice even without the requirement of T cells. Unexpectedly, they also found that the activated macrophages were able to eat cancer cells even in the presence of high levels of CD47.

To understand the molecular basis of this phenomenon, the team traced the metabolic activity of macrophages and determined that activated macrophages began to utilize both glutamine and glucose as fuel to support the energy requirements needed for them to eat cancer cells. This rewiring of the macrophages metabolism was necessary for CpG to be effective, and the researchers say these findings point to the importance of macrophage metabolism in determining the outcome of an immune response.

Related news.

Abstract:

Macrophages enforce antitumor immunity by engulfing and killing tumor cells. Although these functions are determined by a balance of stimulatory and inhibitory signals, the role of macrophage metabolism is unknown. Here, we study the capacity of macrophages to circumvent inhibitory activity mediated by CD47 on cancer cells. We show that stimulation with a CpG oligodeoxynucleotide, a Toll-like receptor 9 agonist, evokes changes in the central carbon metabolism of macrophages that enable antitumor activity, including engulfment of CD47+cancer cells. CpG activation engenders a metabolic state that requires fatty acid oxidation and shunting of tricarboxylic acid cycle intermediates for de novo lipid biosynthesis. This integration of metabolic inputs is underpinned by carnitine palmitoyltransferase 1A and adenosine tri-phosphate citrate lyase, which, together, impart macrophages with antitumor potential capable of overcoming inhibitory CD47 on cancer cells. Our findings identify central carbon metabolism to be a novel determinant and potential therapeutic target for stimulating antitumor activity by macrophages.

Journal Reference:
Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47−mediated 'don't-eat-me' signal, Nature Immunology (2019). DOI: 10.1038/s41590-018-0292-y , https://www.nature.com/articles/s41590-018-0292-y

 

[Ygggdrasil]

In general, the idea of using the body's immune system to fight cancer, called cancer immunotherapy, is an approach that has shown great promise and is a major focus of cancer research. The researchers who developed the first cancer immunotherapy approach were just awarded the 2018 Nobel Prize in Physiology or Medicine for their work (https://www.nobelprize.org/prizes/medicine/2018/summary/).

The work described in the OP may have applications toward developing vaccines against cancer as researchers in that area use a similar approach as that described in the OP: https://www.physicsforums.com/threads/new-cancer-research-at-stanford.938605/