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Related Experiment Videos

Aged mice develop protective antitumor immune responses with appropriate costimulation.

Joseph Lustgarten1, Ana Lucia Dominguez, Marilyn Thoman

  • 1Sidney Kimmel Cancer Center, San Diego, CA 92121, USA. jlustgarten@skcc.org

Journal of Immunology (Baltimore, Md. : 1950)
|September 24, 2004
PubMed
Summary

Aging impairs CD8(+) T cell immunity, but this decline is reversible. Providing efficient costimulation, such as through CD80 expression or anti-OX40 treatment, restores antitumor responses and memory in aged mice.

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Area of Science:

  • Immunology
  • Aging Research
  • Cancer Immunology

Background:

  • CD8(+) T cell effector function declines with age, previously thought to be intrinsic.
  • Recent evidence suggests the aged lymphoid microenvironment alters stimulatory signals, impacting T cell function.

Purpose of the Study:

  • To investigate the impact of costimulation on immune responses against lymphoma in aged mice.
  • To determine if enhanced costimulation can restore antitumor immunity and memory in aging populations.

Main Methods:

  • Comparison of immune responses in young and aged mice against BM-185 pre-B cell lymphoma expressing EGFP.
  • Utilized BM-185-EGFP engineered to express CD80 (BM-185-EGFP-CD80) to assess costimulatory effects.
  • Administered agonist anti-OX40 mAb in conjunction with tumor cells to aged mice.

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Main Results:

  • Aged mice failed to mount protective immune responses against BM-185-EGFP, unlike young mice.
  • BM-185-EGFP-CD80 induced tumor rejection in both young and aged mice.
  • While young mice developed memory responses, aged mice did not, unless treated with anti-OX40 mAb.
  • Anti-OX40 mAb treatment enabled aged mice to develop robust, long-lasting memory responses.

Conclusions:

  • The aged T cell repertoire retains the capacity for strong antitumor and memory responses.
  • Efficient costimulation is crucial for overcoming age-related deficits in T cell immunity.
  • These findings support the development of novel vaccination strategies to enhance tumor immunity in the elderly.