Promising tests in cancer immunotherapy


A novel immunotherapy to fight cancer

(UCLouvain press release)

Sophie Lucas, researcher at the de Duve at UCLouvain, and her team succeeded in neutralizing a molecule that blocks immune responses against cancer. The UCLouvain scientists discovered that this novel form of immunotherapy induces tumor regressions by strongly increasing the efficacy of another well-known immunotherapeutic approach. Their discovery, very promising for the fight against cancer, is published in the prestigious scientific journal Nature Communications.

Cancer immunotherapy consists in manipulating immune cells in patients to fight cancer. The specificity of immunotherapy is to stimulate or boost healthy immune cells in the human body, so these cells can in turn kill the cancer cells that form the tumor. Often indeed, anti-tumor immune defenses are paralyzed by cells or molecules that prevent immune cells from killing cancer cells, allowing the tumor to settle and grow.

In 2004, Sophie Lucas, now president of the de Duve Institute at UCLouvain, decided to tackle the following question: “How are anti-tumor immune responses blocked in cancer patients?”. More precisely, she wanted to understand how a very special type of cells called Regulatory T lymphocytes, or Tregs, exert potent “immunosuppression” within tumors. In 2009, the young UCLouvain researcher discovered GARP, a molecule located on the surface of Tregs.

In 2018, Sophie Lucas finally managed to understand the role of GARP: the molecule acts as a messenger for Tregs, by sending inhibitory signals that block immune defenses. She then developed a tool (anti-GARP antibodies) to neutralize the inhibitory messenger and prevent it from sending its paralyzing signal. This important discovery was published in Science. It allowed the team to propose using anti-GARP antibodies as a new immunotherapeutic agent (a new drug) against cancer.

August 2020Nature Communications publishes the results of the first tests carried out by Sophie Lucas and her team to evaluate the new drug. Their conclusions are very promising: the scientists succeeded in neutralizing Tregs in tumor-bearing mice using anti-GARP antibodies. When the inhibitory messenger was neutralized, anti-tumor immune responses were no longer paralyzed and started to eliminate cancer cells. The result? Tumors regressed quickly, provided that the anti-GARP antibodies were combined with another immunotherapy (so-called PD1 blockade proven to work in patients. The bet of Sophie Lucas' team? Combine the two complementary immunotherapies, which act on distinct pathways of the immune system, to increase the efficacy of treatments against cancer. And it worked!

What will happen next? Similar tests will be carried out in cancer patients, with the hope to provide a more effective therapy against cancer.

Tregs expressing GARP are found in human melanoma samples.

Article describing this research

Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer

de Streel G, Bertrand C, Chalon N, Liénart S, Bricard O, Lecomte S, Devreux J, Gaignage M, De Boeck G, Mariën L, Van De Walle I, van der Woning B, Saunders M, de Haard H, Vermeersch E, Maes W, Deckmyn H, Coulie PG, van Baren N and Lucas S

Nat. Commun. (2020) 11:45

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This work was supported by grants from the Fondation contre le Cancer, from the European Research Council (ERC), from the Actions de Recherche Concertées, from the FNRS and from the Région Wallonne.