Harnessing the immune suppressive potential of cancer-associated fibroblasts in gastrointestinal malignancies
The incidence of gastrointestinal malignancies is rising worldwide and novel therapeutic strategies that can treat these patients are warranted. A potential new treatment modality is immunotherapy, in which the patient’s own immune system is used to recognize and eliminate aberrant tumor cells. However, immune evasion by the tumor frequently occurs, inhibiting an effective anti-tumor response and rendering immunotherapy ineffective. The dampening of the anti-tumor response is the topic of active investigation and requires a thorough understanding of the tumor and the micro-environment in which a tumor resides. The tumor micro-environment (TME) consists of endothelial cells, immune cells and cancer-associated fibroblasts (CAFs). CAFs are the most abundant cell type present in the TME and can make up 50-95% of the tumor mass in gastrointestinal malignancies. Moreover, CAFs have shown to play an important role in all aspects of tumor biology, including metastasis, angiogenesis and immune evasion.
The important role for CAFs in suppressing migration and activation of immune cells was recently shown to be partly dependent on signalling via the Transforming Growth Factor beta (TGFβ) pathway. Therefore, our studies focus on TGFβ mediated immunosuppression by CAFs in gastrointestinal malignancies, with a focus on colorectal cancer (CRC). Our main focus resides on the interplay between CAFs and T cells, for which we use close-to-patient models in order to investigate these interactions. The goal of this project is to contribute to the understanding of CAF-mediated immune suppression and identify potential targets that can be exploited in order to further enhance immunotherapeutic interventions for patients with gastrointestinal malignancies.
Tom Harrijvan obtained his Master degree in Medicine (dec-2017) and Biomedical Sciences (april-2018) from the Leiden University Medical Center (LUMC). Afterwards he started his PhD study, as part of the MD/PhD track, where he investigates the immunoregulatory role of cancer-associated fibroblasts in gastrointestinal malignancies under supervision of dr. Luuk Hawinkels (Gastroenterology & Hepatology), dr. Els Verdegaal (Medical Oncology) & prof. dr. James Hardwick (Gastroenterology & Hepatology).
Leids Universitair Medisch Centrum
2333 ZA Leiden
2300 RC Leiden