The HNCP immunotherapy group has made significant contributions to the understanding of SCCHN immunobiology, including key findings related to release and action of tumor-promoting inflammatory signals as well as mechanisms of cancer cell immune escape. Investigators are working towards the development of novel immunotherapies that exploit this knowledge to improve anti-tumor immunity and overall outcomes for SCCHN patients.
- Squamous cell carcinoma of the head and neck (SCCHN) cells can escape recognition by tumor antigen (TA)-specific cytotoxic T lymphocytes (CTL) by downregulation of antigen processing machinery (APM) components, such as the transporter associated with antigen processing (TAP)-1/2 heterodimer. Recent study results show that (TAP)-1/2 downregulation is regulated primarily by an IFN-γ-pSTAT1-mediated signaling pathway, independent of oncogenic STAT3 overexpression in SCCHN cells (Leibowitz et.al., Cancer Immunol Immunother. 2011 Apr;60(4):525-35).
- The microenvironment of aerodigestive cancers contains tumor-promoting inflammatory signals often involved in innate immunity. The epithelial malignancy, squamous cell carcinoma of the head and neck (SCCHN), is characterized by secretion of inflammatory mediators such as human β-defensin (hBD) 3 that can promote tumorigenesis and lymph node metastasis. Findings suggest that hBD3 represents a novel mediator of the chemokine receptor CCR7 expression and anti-apoptotic pathways, which may be exploited by developing SCCHN tumors to enhance their survival and metastasis (Mburu et.al., Carcinogenesis. 2011 Feb;32(2):168-74).
- Aberrant CCR7 expression in a number of human malignancies has been linked to pro-survival,
-invasion and -metastasis pathways. Upregulation of CCR7 in squamous cell carcinoma of the head and neck (SCCHN) patient tumors correlates with lower survival due to metastatic disease. Results support an important biological role for inflammatory NF-κB and AP1 in the regulation of CCR7 expression in metastatic SCCHN. As such, CCR7, NF-κB, and AP1 could be potentially useful therapeutic targets in controlling the progression and metastasis of SCCHN tumors (Mburu et.al., J Biol Chem. 2011 Dec 12).
|Ferris, Robert L., MD, PhD, FACS
|Whiteside, Theresa, PhD
|Vujanovic, Nicola, MD, PhD