Affiliation:
1. 1UT Health San Antonio Long School of Medicine and Graduate School of Biomedical Sciences, The University of Texas, San Antonio, Texas.
2. 2Graduate School of Microbiology and Immunology, Dartmouth College, Hanover, New Hampshire.
3. 3The Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire.
4. 4Dartmouth Health and Dartmouth Cancer Center, Lebanon, New Hampshire.
Abstract
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.
Funder
National institutes of Health
Gmelich Chair
Guyre Funds
Publisher
American Association for Cancer Research (AACR)
Subject
Cancer Research,Immunology