Defining novel mechanisms and regulatory principles between tumors and their microenvironment
Communication of epithelial cells with components of the microenvironment is a prerequisite for normal tissue homeostasis as well as tumor growth. Cancers arise within complex tissue environments that modulate tumor cell proliferation, invasion, and metastatic dissemination on multiple levels. Importantly, cancer cell autonomous, i.e. direct tumor cell-mediated effects caused by intrinsic mutations and rewired gene expression programs, and non-autonomous regulatory pathways arising from the diverse nature of non-tumoral cells of the tumor microenvironment, including platelets, exist, which contribute to tumor progression and immune escape. Given the success as well as the limitations of current immune checkpoint blockade therapies it has become clear that the identification of cancer cell autonomous and non-autonomous factors that influence the composition and activity of the tumor immune microenvironment is essential to comprehend, predict, and improve immune therapy response. Bioinformatical approaches, including techniques such as CIBERSORT and XCell, have allowed for rough estimations of immune cell infiltrates using RNA expression data from bulk tumor tissues. Complementary to this, defining the exact composition as well as localization of immune cells within solid tumors using multispectral imaging (MSI) is an unmet need nowadays, which might help to improve patient stratification and therapy decisions by defining cellular parameters of response to immune checkpoint inhibitors.
Selected publications
Haemmerle M. et al. (2018). The platelet lifeline to cancer: challenges and opportunities. Cancer Cell, 11;33(6):965-983. [Link]
Haemmerle M. et al. (2017). Platelets reduce anoikis and promote metastasis by activating YAP1 signaling. Nat Commun., 21;8(1):310. [Link]
Haemmerle M., Bottsford-Miller J. et al. (2016). Platelet FAK is a critical regulator of tumor growth after withdrawal of anti-angiogenic therapy. J Clin Invest., 2; 126(5):1885-96. [Link] (highlighted in Nature Reviews Clinical Oncology (2016): FAK – new target for anti-angiogenic therapy)
Gutschner T., Hämmerle M., Pazaitis N. et al. (2014). The Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an important pro-tumorigenic factor in hepatocellular carcinoma. Hepatology, 59(5):1900-11. [Link]
Hämmerle M., Gutschner T. et al. (2013). Post-transcriptional destabilization of the liver-specific long non-coding RNA HULC by the IGF2 mRNA-binding protein 1 (IGF2BP1). Hepatology, 58 (5):1703–1712. [Link]
Contact
Principle Investigator
Dr. med. univ. Monika Hämmerle, PhD
Email: monika.haemmerle[at]uk-halle.de
Phone: +49 (0) 345-557 1882
