Pancreatic cancer is a solid tumor made up of cancer cells dispersed within a compartment, the stroma, made up mainly of fibroblasts and macrophages.
The study carried out by Zainab Hussain, within the DISARM team, highlighted the influence of the dialogue between stromal fibroblasts and macrophages on the response to chemotherapies. Her results demonstrate that the presence of fibroblasts within tumors rewires the response of macrophages to chemotherapeutic agents, with a specific transcriptomic signature correlating with a poor prognosis.
This work reinforces the need to assess the global tumoral response to chemotherapies and shed some lights on the link between chemotherapy and immune system modulation, and its practical impact on patient’s management.
INTERVIEW WITH ZAINAB HUSSAIN, CONDUCTED ON 26 FEBRUARY 2024
Can you summarise your article in one sentence?
In pancreatic cancer, macrophages that communicate with cancer-associated fibroblasts during chemotherapy have an increased pro-tumour phenotype, which predicts an unfavourable prognosis.
What impact could your research have on a patient’s treatment?
For pancreatic cancer patients, chemotherapy is currently the only treatment available, which in the majority of cases leads to significant resistance and subsequent relapse. It is therefore essential to find alternative therapies or therapies in combination with chemotherapy to overcome this resistance. This work has enabled us to identify a genetic signature of macrophages caused by communication with cancer-associated fibroblasts under chemotherapy that correlates with poorer patient survival. With further validation of our observations in patient samples, clinicians who identify this signature would be able to suggest a more appropriate therapy. Ultimately, the new genes we have identified in macrophages could be the targets of combination therapy for patients prone to chemoresistance.
What is the next question to be answered?
It will be interesting to study the mechanisms of action of the two genes identified in the macrophage signature, SELENOP and G0S2. Their altered expression could affect their communication with other immune cells such as T lymphocytes and tumour cells, modulating their chemosensitivity? To better understand the contribution of fibroblasts, it would also be important to study the factors expressed by these cells and their impact on the phenotype of anti-immune and pro-tumour macrophages.
Do you have an anecdote about this study?
During the data analysis phase, a large part of the flow cytometry data files were corrupted due to a hard disk crash while I was writing my thesis. Thanks to the help of a very computer-savvy friend, I was able to recover and restore some of the data, but I still had to re-analyse more recent data. It’s always at moments of intense stress that these things happen!
Tell us a little more about yourself: your background, your studies, what attracted you to science?
As a child, I remember being fascinated by questions that didn’t have obvious answers, like asking my mother exactly how many stars there were in our universe and why. This curiosity led me to study science, and one thing led to another and I was drawn to biology and its complexities. After graduating in medicine from the University of Western Ontario in Canada, I decided to continue my studies in France, as I had always been curious about the French way of life. While looking for an internship, I discovered Richard Tomasini’s excellent work and I was lucky enough to join his team from my Masters internship to my PhD.
Where do you go from here? Your future?
During my thesis and after a chance meeting with Dr Mara Sherman at an international conference, I became interested in the work of her team. At the end of my PhD, I was lucky enough to join her team at Memorial Sloan Kettering Cancer Center in New York, where I am currently a postdoctoral fellow. I study the interaction between tumour cells, stromal cells and nerves, particularly in the context of pancreatic cancer metastasis. In the future, I hope to become a teacher-researcher, but above all, I want to contribute to finding a cure for pancreatic cancer.
TO FIND OUT MORE
Hussain Z, Bertran T, Finetti P, Lohmann E, Mamessier E, Bidaut G, Bertucci F, Rego M, Tomasini R.
Cell Commun Signal. 2024 Jan 2;22(1):1. doi: 10.1186/s12964-023-01388-7. PMID: 38167013; PMCID: PMC10759487.