WEBINAR: Activating Cancer Immunity by Reprogramming the Tumour Microenvironment
Sartorius & Science Prize Finalist
Daniele Tauriello, Ph.D.
Institute for Research in Biomedicine, Spain | Postdoctoral Fellow
Metastatic cancer cells must reprogram the tumour stroma, or tumour microenvironment, before they can metastasize. Tumours must also contend with the immune system before they can spread. If the road to metastasis is full of obstacles, how is it so common? The answer probably lies in the fact that as cancer cells reorganize their environment, they thoroughly manipulate the stroma to not just shut down any recruited immune cells, but to suppress the mobilization of an effective immune response in the first place.
I generated a mouse model of metastatic colorectal cancer that recapitulates relevant characteristics of human metastatic disease, and that can be transplanted by the use of tumour organoids. Leveraging this immunocompetent platform, we demonstrated the role of TGFβ signaling in suppressing the immune response. Blockade of this pathway led to T-cell-mediated immunity, preventing metastatic initiation in the liver.
Moreover, TGFβ blockade rendered late-stage metastases susceptible to immune checkpoint inhibition treatment. Whereas this form of therapy failed by itself—as it has in the clinic for most patients with metastatic colorectal cancer—the combined therapy synergized to cure the majority of mice with advanced liver metastases. Thus, our results indicate that immunotherapies can be made more efficient for a wider range of patients by understanding and neutralizing immune evasion mechanisms in the tumour microenvironment.
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