Cancer cell - fibroblast crosstalk signature promotes macrophage recruitment via HB-EGF and stromal EGFR/MEK signalling

Giangreco, G.; Rullan, A.; Naito, Y.; Biwas, D.; Liu, Y.-H.; Hooper, S.; Nenclares, P.; Bhide, S.; Cheang, M.; Chakravarty, P.; Hirata, E.; Swanton, C.; Melcher, A.; Harrington, K.; Sahai, E.

doi:10.1101/2023.07.13.548733

bioRxiv · 10.1101/2023.07.13.548733

Cancer cell - fibroblast crosstalk signature promotes macrophage recruitment via HB-EGF and stromal EGFR/MEK signalling

Giangreco, G.·Rullan, A.·Naito, Y.·Biwas, D.·Liu, Y.-H.·Hooper, S.·Nenclares, P.·Bhide, S.·Cheang, M.·Chakravarty, P.·Hirata, E.·Swanton, C.·Melcher, A.·Harrington, K.·Sahai, E.

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Abstract

Interactions between cells in the tumor microenvironment (TME) shape cancer progression and patient outcomes. To gain new insights into how the TME influences cancer outcomes, we derive gene expression signatures indicative of signaling between stromal fibroblasts and cancer cells, and demonstrate their prognostic significance in multiple and independent squamous cell carcinoma cohorts. By leveraging information within the signatures, we discover that the HB-EGF/EGFR/MEK axis represents a hub of tumor - stroma crosstalk, promoting the expression of CSF2 and LIF and favoring the recruitment of macrophages. Together these analyses demonstrate the utility of our approach for interrogating the extent and consequences of TME crosstalk.

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Giangreco, G., Rullan, A., Naito, Y., Biwas, D., Liu, Y.-H., Hooper, S., Nenclares, P., Bhide, S., Cheang, M., Chakravarty, P., Hirata, E., Swanton, C., Melcher, A., Harrington, K., Sahai, E.. 2023-07-14. Cancer cell - fibroblast crosstalk signature promotes macrophage recruitment via HB-EGF and stromal EGFR/MEK signalling. https://doi.org/10.1101/2023.07.13.548733

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