Pomegranate metabolite improves the function of immune cells to fight cancer

Pomegranate metabolite improves the function of immune cells to fight cancer

As part of an interdisciplinary project at the LOEWE Center Frankfurt Cancer Institute (FCI), researchers from the Georg Speyer House in Frankfurt am Main and the Goethe University Frankfurt have succeeded in identifying a new approach for the treatment of colon cancer. In preclinical models and studies on human immune cells, they found that urolithin A, a metabolite of pomegranate, sustainably improves the function of immune cells in the fight against cancer. After treatment with Urolithin A, tumor-fighting immune cells become T memory stem cells, which, due to their ability to divide, constantly supply the immune system with rejuvenated, not exhausted T cells.

Colorectal cancer remains a disease with high mortality rates in advanced stages. Numerous research results have improved early detection and therapy in recent years, but unfortunately not all patients respond adequately to new therapeutic approaches. Current research results indicate that a characteristic of tumor diseases is a dysfunction of the immune system: immune cells that are supposed to fight the tumor are systematically suppressed by the tissue surrounding the tumor, the tumor microenvironment. This limits the function of T cells, our body's natural immune response against cancer, allowing the tumor to grow and spread uncontrollably.

The research team led by Professor Florian Greten, Institute for Tumor Biology and Experimental Therapy and Goethe University Frankfurt, has now come a decisive step closer to a possible solution to the problem. The researchers showed that urolithin A induces a biological pathway that recycles and renews mitochondria, the cell's "powerhouses" in T cells, through a process known as mitophagy. Aged and damaged mitochondria in the T cells are removed and replaced with new, functional ones. This changes the genetic program of the T cells, which allows them to fight the tumor better. The researchers demonstrated the therapeutic potential of urolithin A in two ways: Firstly, urolithin A can be used in the preclinical model as a food that limits tumor growth and even works synergistically with existing immunotherapies. On the other hand, the benefits of urolithin A have also been observed in human T cells. In vitro treatment with urolithin A “rejuvenates” human T cells and produces memory T stem cells in the laboratory.

Our findings are particularly exciting because the focus is not on the tumor cell, but on the immune system, the natural defense against cancer. In reality, there is still a lack of reliable therapeutic approaches for colon cancer patients. By potentially improving combination therapy with existing immunotherapies, the study opens up useful possibilities for further clinical use. We hope to be able to sustainably improve the treatment of colon cancer, but also other types of cancer.”

Dominic Denk, MD, first author, doctor at the University Hospital Frankfurt

Building on these findings, the researchers want to continue their successful collaboration: future clinical studies will examine the use of urolithin A in people with colon cancer.

Professor Greten, director of the Georg Speyer House and spokesman for the Frankfurt Cancer Institute, emphasizes the necessary teamwork: "This work proves once again how successful the FCI's interdisciplinary concepts are. We are very pleased that we can now quickly transfer our results to the clinic and are looking forward to the upcoming clinical studies with great excitement."

Source:

Goethe University Frankfurt

Reference:

Denk, D., et al. (2022) Expansion of memory T stem cells with superior antitumor immunity through urolithin A-induced mitophagy. Immunity. doi.org/10.1016/j.immuni.2022.09.014.

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