Alexandra Garancher: understanding a tumor's immune environment to better eliminate it

As is often the case in molecular biology, it all starts with petri dishes and mice. For cancer researcher Alexandra Garancher, it was an L3 internship on cell differentiation that gave her a taste for laboratory research. It was the beginning of a vocation that shows no signs of waning 15 years later. Today, the young neuro-oncology biologist is a specialist in medulloblastoma (MB). Nothing to do with the name of a villain in the latest Marvel movie: it's a malignant tumor that develops in the cerebellum of young children.

As early as her Masters 2 at the Institut Curie, her research showed the links between the mechanisms regulating cell differentiation and the development of medulloblastomas. Her results were extended during her thesis, when she identified a key player in oncogenesis and proposed an inhibitor to limit tumor development. The result was a publication in Cancer Cell, and her first collaboration with a laboratory in the United States. This opening on the other side of the Atlantic is not about to close anytime soon, as the young doctor goes on to complete a six-year post-doctorate at the Sanford Burnham Prebys Medical Discovery Institute in San Diego, California.

Numerous research platforms

For Alexandra Garancher, the challenge is to extend her research from the tumor cell to the tumor's entire immune environment. In other words, to understand how the immune system interacts with tumor cells, and how it might play a role in tumor elimination. A branch of cancer treatment research known as immunotherapy. More specifically, her research focuses on immune evasion mechanisms: since MB is able to escape the immune system, how do we make it visible again to T lymphocytes? Her research led her to find a cytokine capable of restoring a surface protein that had disappeared from the cancer cell (rendering it undetectable to T lymphocytes). This enabled her to restore anti-tumor immunity and the efficacy of certain therapeutic antibodies. The result is an article in Nature Neuroscience and a patent!

" Alongside this research, I really enjoyed taking part in a wide-ranging collaboration with the medical profession. As my work used patients' cancer cells grafted onto mice, we were able to test the efficacy of treatments in the laboratory. Oncologists, surgeons, bioinformaticians, we then worked together to make choices about the patient's treatment ", explains the researcher. An American experience that she wants to continue at the IRCM, where she has held a position since February 2021. Indeed, while her applications in France lead to several offers, it's the research environment in Montpellier that weighs on her choice. Coming to the IRCM also meant taking advantage of its links with the CHU, the Biocampus and its many research platforms," explains Alexandra Garancher. When I applied, the IRCM also offered me the chance to spend a week here. I experienced a collaborative workspace that made me want to stay.

"Often more aggressive and resistant

When you ask her about what's next, you realize just how ambitious she is. " I've been working on MB for 10 years. The idea is to see if I can extend my discoveries to other tumors. In particular, to breast cancer metastases. I'd also like to continue my research into the immune environment, in particular understanding the effect of therapies (radiotherapy, chemotherapy and immunotherapy) on cancer progression." Because while these therapies act on tumors, they can also have negative effects on treatment. Radiotherapy, for example, kills immune cells, thereby reducing the body's ability to defend itself. Unstoppable, the researcher suggests another line of research: improving the action of T lymphocytes on brain tumours, to enable a better immune response.

She won't be able to do it all on her own. Within the IRCM, she intends to set up her own research team to carry out these projects. And she is already looking for other sources of funding, notably by applying to the ATIP-avenir and the ERC (European Research Council Research). The scale of the task doesn't seem to dampen his tenacity: " We still have a lot to learn about the role of the tumor's environment in the evolution of cancers, while the emergence of recurrent tumors and metastases, often more aggressive and resistant, sometimes have more dramatic consequences than the primary tumor ".