Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer
A recent "Cancer Cell" paper by the Bodenmiller group (IMHS) demonstrates the importance and prognostic value of cancer-associated fibroblast heterogeneity in non-small cell lung cancer and show that different CAF types are either pro- or anti-tumour.
Cancer-associated fibroblasts (CAFs) are a highly heterogeneous cell type found in tumours. Distinct CAF subsets have been found to make vital contributions to tumour progression as well as patient prognosis. Applying their recently published CAF classification system to a clinical cohort of over 1,000 patients, researchers of the Bodenmiller group at IMHS were able to identify good and poor prognostic CAF types.
Using imaging mass cytometry (IMC), a highly multiplexed spatial proteomics technique, they showed that CAFs are strong independent factors for patient prognosis. They found that the good prognostic CAF types were associated with a high presence of immune cells in the tumour, suggesting their support of a robust anti-tumour directed immune response. Making use of their spatial single-cell data, they discovered that tumour supporting CAFs are located in close vicinity to tumour cells and were associated with a reduced number of anti-tumour immune cells. They were further able to show that one CAF type exerted its tumour support by creating a barrier around the tumour that actively hampers immune cells from reaching the tumour. They also found correlations between different poor prognostic CAF types and the occurrence of metastasis as well as therapy resistance.
The study provides a valuable resource for the study of CAF heterogeneity and suggests directions for further studies in the field of precision medicine to allow the exploitation of CAFs as potential targets in cancer therapy in the future.
Link to the paper in external page "Cancer Cell".