Inflammation is a double-edged sword in the establishment of anti-tumor immunity. Chronic inflammation suppresses immune responses and promotes tumor growth and survival. In contrast, acute inflammation is critical to the establishment of any adaptive (long-term) immune response against cancer. My laboratory studies both of these aspects of inflammation in the hope of discovering ways to overcome/alter chronic inflammation and promote acute inflammation. Our work is divided into three major themes:
Tumor-induced chronic inflammation:
Tumor cells secrete factors that induce chronic inflammation. One of these factors is peroxiredoxin 1 (Prx1). Prx1 expression is elevated in various cancers and is associated with poor clinical outcome and diminished patient survival. We have shown that Prx1 secretion by prostate tumors promotes a chronic inflammatory, pro-tumorigenic microenvironment (Riddell et al, 2010). In addition we have demonstrated that inhibition of Prx1 expression in prostate tumors results in reduced tumor growth and a reduction in chronic inflammation (Riddell et al. 2011). The current focus of the lab is determining how Prx1 contributes to tumor growth and the mechanism behind increased Prx1 expression in tumor cells.
Role of Acute Inflammation:
The second major project in the lab is focused on understanding the role of acute inflammation, induced by cancer therapies, in the development of immune responses against cancer. Our long-term goal is to develop treatments that can control both primary tumor growth and distant metastases. To generate acute inflammation in a tumor setting, we use photodynamic therapy (PDT), which is a FDA approved treatment for malignant and non-malignant diseases that used a photo-reactive drug in combination with light to generate reactive oxygen. The release of reactive oxygen results in tumor cell death, which leads to induction of acute local inflammation. (To learn more about PDT go to http://www.roswellpark.org/specialized-services/photodynamic-therapy). My lab has shown that PDT activates innate immune cells, such as dendritic cells (Gollnick et al, Lasers Surg. Med., 2006), neutrophils (Kousis et al., Cancer Res. 2007) and natural killer cells (Kabingu et al, Br. J. Cancer, 2007), and that these cells control the function of tumor specific cytolytic T cells and their ability to control distant tumors. We are currently investigating which inflammatory mediators are critical to the induction of anti-tumor immunity following PDT.
PDT-Treated tumor Cells Act as Anti-Tumor Vaccines:
A second major focus of the lab stems from our novel findings that PDT-treated tumor cells are able to act as anti-tumor vaccines (Gollnick et al, Cancer Res., 2002). Since this finding we have gone one to demonstrate that PDT vaccines are effective adjuvants when combined with surgery and we are currently developing clinical trials to test the use of PDT vaccines in combination with surgery to treat melanoma and head and neck carcinomas. We are also working to understand the “danger signals” generated by PDT treatment of tumor cells that leads to activation of the immune response.