Innate immunity receptor (TLR9) in cancer

​Description of Research

Toll-like receptor-9 (TLR9) is an innate immune system DNA-receptor. Initially, it was thought that TLR9 only senses microbe-derived DNA. It is, however, now well estab-lished that TLR9 can recognize also host-derived DNA, and this recognition contributes to the pathological inflammation detected in many autoimmune diseases as well as cancer. We showed recently that tumor TLR9 can be used as a prognostic marker in triple-negative breast cancer. The molecular dissection of this pathway may reveal novel biomarkers and drug targets for many cancer types, and also help to understand why hypoxia-inducing therapy or events that affect TLR9 expression in tumors may actually promote tumor growth and spread.

List of Personnel

Maija Valta, MD, PhD

Jouko Sandholm, PhD

Tamiko Ishizu, Doctoral candidate

Yvonne Konkol, Doctoral candidate

Nataliia Petruk, Doctoral candidate

Alejandra Verhassel, Doctoral candidate

Arafat Siddiqui, Doctoral candidate

Sanni Tuominen, Doctoral candidate

Lauri Närhi, Undergraduate student

Selected Publications

Tuomela J, Sandholm J, Kaakinen M, Hayden K, Haapasaari K-M, Jukkola-Vuorinen A, Kauppila J, Lehenkari P, Harris KW, Graves D, Selander KS. Telomeric G-quadruplex-forming DNA fragments induce TLR9-mediated and LL-37-regulated invasion in breast cancer cells in vitro. Breast Cancer Res. Treat.2016;155:261-71.

Valta M, Fagerlund K, Suominen M, Halleen J, Tuomela J. Importance of microenvironment in preclinical models of breast and prostate cancer. World J Pharmacol. 2015; 4(1):47-57.

Tuomela J, Härkönen P. Tumor models for prostate cancer exemplified by fibroblast growth factor 8-induced tumorigenesis and tumor progression. Reprod Biol. 2014;14(1):16-24.

Tuomela J, Sandholm J, Kaakinen M, Patel A, Kauppila JH, Ilvesaro J, et al. DNA from dead cancer cells induces TLR9-mediated invasion and inflammation in living cancer cells. Breast Cancer Res Treat. 2013.

Tuomela J, Sandholm J, Karihtala P, Ilvesaro J, Vuopala KS, Kauppila JH, et al. Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer. Breast Cancer Res Treat. 2012;135(2):481-93.