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Considerations and Approaches for Cancer Immunotherapy in the Aging Host
Carlos O Ontiveros1, Clare E Murray1, Grace Crossland2,3
1UT Health San Antonio Long School of Medicine and Graduate School of Biomedical Sciences, The University of Texas, San Antonio, Texas.
Abstract:
Advances in cancer immunotherapy are improving treatment successes in many distinct cancer types. Nonetheless, most tumors fail to respond. Age is the biggest risk for most cancers, and the median population age is rising worldwide. Advancing age is associated with manifold alterations in immune cell types, abundance, and functions, rather than simple declines in these metrics, the consequences of which remain incompletely defined. Our understanding of the effects of host age on immunotherapy mechanisms, efficacy, and adverse events remains incomplete. A deeper understanding of age effects in all these areas is required. Most cancer immunotherapy preclinical studies examine young subjects and fail to assess age contributions, a remarkable deficit given the known importance of age effects on immune cells and factors mediating cancer immune surveillance and immunotherapy efficacy. Notably, some cancer immunotherapies are more effective in aged versus young hosts, while others fail despite efficacy in the young. Here, we review our current understanding of age effects on immunity and associated nonimmune cells, the tumor microenvironment, cancer immunotherapy, and related adverse effects. We highlight important knowledge gaps and suggest areas for deeper enquiries, including in cancer immune surveillance, treatment response, adverse event outcomes, and their mitigation.
Insights
Cancer immunotherapy effectiveness varies with age due to complex immune changes. Further research is crucial to understand and optimize treatments for older cancer patients.
Area of Science:
- Immunology
- Oncology
- Gerontology
Background:
- Cancer immunotherapy shows promise but faces challenges with non-responsive tumors.
- Increasing global median age highlights the need to understand age-related immune system alterations.
- Current knowledge on host age's impact on cancer immunotherapy efficacy and safety is incomplete.
Approach:
- This review synthesizes current understanding of age-related changes in immunity, non-immune cells, and the tumor microenvironment.
- It examines the influence of host age on cancer immunotherapy mechanisms, treatment outcomes, and adverse events.
- The review identifies critical knowledge gaps in age-related cancer immunology and immunotherapy.
Key Points:
- Advancing age causes complex immune cell alterations, not just decline, impacting cancer immune surveillance.
- Preclinical cancer immunotherapy studies often neglect age, despite its known influence on immune responses.
- Host age can differentially affect the efficacy of various cancer immunotherapies, with some being more effective in aged hosts.
Conclusions:
- A comprehensive understanding of age's role in cancer immunotherapy is essential for improving treatment success and mitigating adverse events.
- Further research is needed to explore age-specific effects on cancer immune surveillance, treatment response, and adverse event management.
- Optimizing cancer immunotherapy for diverse age groups requires addressing the identified knowledge gaps.
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