Decreases in macrophage mediated antitumor activity with aging

Area of Science:

• Immunology
• Aging Research
• Cancer Biology

Background:

• Immunotherapy using biological response modifiers shows differential efficacy in young versus aged tumor-bearing mice.
• Enhanced survival and tumor growth inhibition were observed in young mice, but not in aged mice.

Purpose of the Study:

• To investigate the hypothesis that age-associated defects in macrophages (M phi) contribute to the reduced efficacy of immunotherapy in aged mice.
• To directly assess the antitumor activity and cytokine production of peritoneal M phi from young and aged mice.

Main Methods:

• Peritoneal M phi were isolated from young and aged mice.
• M phi were activated in vitro using interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS).
• Antitumor activity, tumor necrosis factor (TNF), interleukin-1 (IL-1), and nitric oxide production were measured.

Main Results:

• M phi from aged mice exhibited significantly reduced in vitro antitumor activity compared to M phi from young mice.
• Activated M phi from aged mice showed diminished capacity to produce TNF, IL-1, and nitric oxide.
• These findings correlate with the in vivo observations of immunotherapy efficacy.

Conclusions:

• Peritoneal macrophages from aged mice possess an intrinsic defect that impairs their antitumor potential.
• This age-related M phi defect is a key factor limiting the effectiveness of immunotherapy in older individuals.
• Restoring M phi function may be a therapeutic strategy to improve cancer treatment outcomes in the elderly.