Aging and immunotherapies: New horizons for the golden ages

Abstract

The life expectancy of the world's elderly population (65 and older) continues to reach new milestones with older individuals currently comprising greater than 8.5% (617 million) of the world's population. This percentage is predicted to approach 20% of the world's population by 2050 (representing 1.6 billion people). Despite this amazing feat, many healthcare systems are not equipped to handle the multitude of diseases that commonly manifest with age, including most types of cancers. As the world's aging population grows, cancer treatments continue to evolve. Immunotherapies are a new drug class that has revolutionized our ability to treat previously intractable cancers; however, their efficacy in patients with compromised immune systems remains unclear. In this review, we will discuss how aging-associated losses in immune homeostasis impact the efficacy and safety of immunotherapy treatment in preclinical models of aging. We will also discuss how these findings translate to elderly patients receiving immunotherapy treatment for refractory and relapsed cancers, as well as, strategies that could be explored to improve the efficacy of immunotherapies in aged patients.

T cell immune awakening in response to immunotherapy is age-dependent

“…For example, TCR-based biomarkers need to consider how age affects TCR repertoire evolution following treatment and therapies that require more diverse T cell repertoires may be less effective in older patients. Critically, the inconsistent recruitment of older patients into clinical trials has led to the development of treatments largely in younger patients who typically have different biological and physiological responses [ 23 , 24 ]. As our data highlight, future work should focus on ensuring the inclusion of patients ≥70 years of age in immunotherapy clinical trials and the reporting of age-group specific survival outcomes.…”

Cancer and aging: A call to action

“…One such challenge is over-coming the limited efficacy of immunotherapies in older cancer patients that results from multiple factors, including immunosenescence—immunological decline characterized by an increase in memory T cells and decreased peripheral blood naïve cells. 69 Although immunotherapies are revolutionizing treatment landscape, the efficacy of immunotherapy appears to decrease with age, 70 and older adults are more likely to experience immunotherapy-related adverse events, 71 which often result in early discontinuation of treatment. 72 Clearly, it is imperative that we elucidate the dynamic interplay of aging, cancer, and immunosenescence.…”

Clinical perspectives on the age-related increase of immunosuppressive activity

“…There are many studies indicating that the efficiency of immunotherapeutic treatments becomes diminished in elderly people [ 174 ]. The senescence of the immune system is a major difficulty in the activating immunotherapies, e.g., in the treatments of cancer patients [ 175 , 176 ].…”