Abstract Title

Th1 cytokines TNF-α and IFN-γ promote cell death in human prostate cancer cell lines via an apoptotic mechanism.

Abstract

A recent clinical vaccine trial to treat early breast cancer prior to surgery induced strong T cell-dependent immune responses characterized by the production of Th1 cytokines including Interferon-gamma (IFN-γ). Of 27 vaccinated subjects, 5 showed complete regression of tumor by the time of surgery. In vitro studies indicated that Th1 cytokine production might have a direct killing effect on breast cancer cells. We therefore sought to determine whether other carcinoma types were also sensitive to Th1 cytokines, a fact that might indicate their sensitivity to similar therapeutic vaccination. We therefore examined the effects of the two principal Th1 cytokines, IFN-γ and TNF-α on 3 common prostate cancer cell lines including LnCap, PC3 and DU145. Each cell line was incubated in tissue culture with cytokines for up to 5 days. Addition of the Alamar Blue dye during the last hours of culture indicated that cytokine-treated cells displayed sharply reduced metabolic activity. Likewise, microscopic observation of cells indicated signs of cell death. Vital staining indicated less viable cells in Th1 cytokine-treated groups compared to untreated controls. Finally, Flow cytometry analyisis of cytokine treated cells showed evidence of enhanced apoptosis compared with untreated cells, indicating induction of programmed cell death in cytokine-treated cells. These data show that prostate cancer may be amenable to vaccination that induces strong Th1 type immunity. Enhancing effects of some anti-cancer drugs were also examined.

Modified Abstract

Anti-cancer vaccine effects observed in early breast cancer are probably mediated in part through the action of T cell-secreted cytokines Interferon-gamma (IFN-γ) and Tumor necrosis factor alpha (TNF-α). We therefore sought to determine whether other types of cancer such as prostate cancer were likewise susceptible to these same cytokines. We tested 3 different prostate cancer cell lines for sensitivity to paired combination of IFN-γ and TNF-α. We observed evidence of impaired metabolic activity, fewer viable cells and evidence of apoptotic cell death induced by cytokines. These studies indicate that anti-cancer vaccines that stimulate production of these cytokines may be effective for prostate cancer.

Research Category

Biomedical Sciences

Primary Author's Major

Biology

Mentor #1 Information

Gary K. Koski, Ph.D.

Mentor #2 Information

Lori Showalter, Ph.D.

Presentation Format

Poster

Start Date

March 2016

Research Area

Medicine and Health Sciences | Translational Medical Research

This document is currently not available here.

Share

COinS
 
Mar 15th, 1:00 PM

Th1 cytokines TNF-α and IFN-γ promote cell death in human prostate cancer cell lines via an apoptotic mechanism.

A recent clinical vaccine trial to treat early breast cancer prior to surgery induced strong T cell-dependent immune responses characterized by the production of Th1 cytokines including Interferon-gamma (IFN-γ). Of 27 vaccinated subjects, 5 showed complete regression of tumor by the time of surgery. In vitro studies indicated that Th1 cytokine production might have a direct killing effect on breast cancer cells. We therefore sought to determine whether other carcinoma types were also sensitive to Th1 cytokines, a fact that might indicate their sensitivity to similar therapeutic vaccination. We therefore examined the effects of the two principal Th1 cytokines, IFN-γ and TNF-α on 3 common prostate cancer cell lines including LnCap, PC3 and DU145. Each cell line was incubated in tissue culture with cytokines for up to 5 days. Addition of the Alamar Blue dye during the last hours of culture indicated that cytokine-treated cells displayed sharply reduced metabolic activity. Likewise, microscopic observation of cells indicated signs of cell death. Vital staining indicated less viable cells in Th1 cytokine-treated groups compared to untreated controls. Finally, Flow cytometry analyisis of cytokine treated cells showed evidence of enhanced apoptosis compared with untreated cells, indicating induction of programmed cell death in cytokine-treated cells. These data show that prostate cancer may be amenable to vaccination that induces strong Th1 type immunity. Enhancing effects of some anti-cancer drugs were also examined.