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Updated: Aug 23, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Age-dependent differences in the efficacy of cancer immunotherapy in C57BL and AKR mouse strains
Tanya Kaptzan1, Ehud Skutelsky, Orit Itzhaki
1Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, 69978, Israel.
Abstract:
While tumor incidence increases with age, tumor growth and metastasis often proceed at a slower rate in aged organisms. The mechanisms underlying this age-related reduced tumor development may suggest therapeutic modalities appropriate for the aged. Decreased tumor aggressiveness in the old was shown to be related to altered immune response. Consequently, the aim of the present study was to assess whether cancer immunotherapy has an age-dependent effect. Only a few studies have compared cancer immunotherapy efficiency as a function of age, most showing lower inhibition in older animals. In the present study, we tested the effect of two immunomodulators, levamisole and BCG, on two tumors, B16 melanoma and AKR lymphoma, in mice of different ages. We demonstrated a higher efficiency of immunotherapy in aged as compared to young mice, particularly at low immunomodulator doses. While decreased T cell function during aging is apparently established, nonspecific immunity is more preserved or even enhanced in later life. We found an increased number of macrophages in tumors of old compared to young mice and an increase in MAC-1+ cells in old levamisole-treated compared to non-treated mice. The stronger therapeutic effect of this immunomodulator in old mice might thus be due to an increased macrophage-mediated anti-tumoral effect.
Insights
Cancer immunotherapy is more effective in aged mice, particularly at lower doses. This enhanced efficacy in older animals may stem from increased macrophage activity, suggesting new therapeutic strategies for the elderly.
Area of Science:
- Immunology
- Oncology
- Gerontology
Background:
- Tumor incidence rises with age, yet tumor growth and metastasis slow down in older individuals.
- Age-related immune system alterations influence tumor development and may impact cancer treatment efficacy.
Purpose of the Study:
- To investigate the age-dependent effects of cancer immunotherapy.
- To compare the efficacy of immunomodulators in young versus aged mice.
Main Methods:
- Administered levamisole and BCG immunomodulators to young and aged mice bearing B16 melanoma or AKR lymphoma.
- Assessed tumor development and immune cell populations, focusing on macrophages and MAC-1+ cells.
Main Results:
- Immunotherapy demonstrated higher efficacy in aged mice compared to young mice, especially at low immunomodulator doses.
- Aged mice exhibited increased macrophage numbers within tumors.
- Levamisole treatment in aged mice led to a higher proportion of MAC-1+ cells, suggesting enhanced macrophage activity.
Conclusions:
- Cancer immunotherapy can be more effective in aged individuals, contrary to some previous findings.
- Enhanced immunotherapy efficacy in older mice may be attributed to preserved or enhanced non-specific immunity, particularly macrophage-mediated anti-tumoral effects.
- Findings suggest potential for age-specific immunotherapy strategies targeting macrophage pathways.
