Age-Induced Changes in Anti-Tumor Immunity Alter the Tumor Immune Infiltrate and Impact Response to Immuno-Oncology Treatments

Authors

Suzanne I Sitnikova
Jennifer A Walker
Laura B Prickett
Michelle Morrow
Viia E Valge-Archer
Matthew J Robinson
Robert W Wilkinson
Simon J Dovedi

Publication Date

1-1-2023

Journal

Frontiers in Immunology

Abstract

INTRODUCTION: Immuno-oncology (IO) research relies heavily on murine syngeneic tumor models. However, whilst the average age for a cancer diagnosis is 60 years or older, for practical purposes the majority of preclinical studies are conducted in young mice, despite the fact that ageing has been shown to have a significant impact on the immune response.

METHODS: Using aged (60-72 weeks old) mice bearing CT26 tumors, we investigated the impact of ageing on tumor growth as well as the immune composition of the tumor and peripheral lymphoid organs.

RESULTS: We found many differences in the immune cell composition of both the tumor and tumor-draining lymph node between aged and young mice, such as a reduction in the naïve T cell population and a decreased intratumoral CD8/Treg ratio in aged animals. We hypothesized that these differences may contribute to impaired anti-cancer immune responses in aged mice and therefore assessed the anti-tumor efficacy of different IO therapies in aged mice, including both co-stimulation (using an anti-OX40 antibody) and immune checkpoint blockade (using anti-PD-L1 and anti-CTLA-4 antibodies). Whilst aged mice retained the capacity to generate anti-tumor immune responses, these were significantly attenuated when compared to the responses observed in young mice.

DISCUSSION: These differences highlight the importance of age-related immunological changes in assessing and refining the translational insights gained from preclinical mouse models.

Keywords

Mice, Animals, Neoplasms, Immunotherapy