Regulatory T cells and Toll-like receptors in cancer immunotherapy
Rongfu Wang, Ph.D., received the award for his research on regulatory T cells and their functional regulation by Toll-like receptor signaling. CD4+ regulatory T (Treg) cells form a vital arm of the immune system that is responsible for controlling rogue immune responses and autoimmunity. Unfortunately, Treg cells also suppress desired antitumor immune responses, rendering vaccination and other forms of immunotherapy completely ineffective. Dr. Wang and his co-workers were the first to identify the natural ligands expressed by tumor cells that activate Treg cells as well as MHC class I-restricted EBNA1 ligands for CD8+ T cell recognition. The cornerstone of Dr. Wang’s research on Treg cells was his recent breakthrough discovery that certain ligands (comprising a stretch of guanosine-containing oligonucleotides) can bind specifically to human Toll-like receptor 8 (TLR8) on Treg cells and turn off their suppressive function. Thus, treatment of Treg cells with TLR8 ligands offers a novel means to enhance immune responses against cancer and infectious diseases.
Dr. Wang’s nomination was based on the following publications:
Wang HY, Lee DA, Peng G, Guo Z, Li Y, Kiniwa Y, Shevach EM, Wang RF. Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity. 2004 Jan;20(1):107-18.
Voo KS, Fu T, Wang HY, Tellam J, Heslop HE, Brenner MK, Rooney CM, Wang RF. Evidence for the presentation of major histocompatibility complex class I-restricted Epstein-Barr virus nuclear antigen 1 peptides to CD8+ T lymphocytes. J Exp Med. 2004 Feb 16;199(4):459-70.
Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, Wang DY, Li Y, Wang HY, Wang RF. Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science. 2005 Aug 26;309(5739):1380-4.