Aging and Immunotherapies: New Horizons for the Golden Ages

Overview

Journal Aging Cancer

Date 2022 Jul 25

PMID 35874875

Authors

Jamie A G Hamilton

Curtis J Henry

Affiliations

Soon will be listed here.

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.

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References

Nosaki K, Saka H, Hosomi Y, Baas P, de Castro Jr G, Reck M . Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: Pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies. Lung Cancer. 2019; 135:188-195. DOI: 10.1016/j.lungcan.2019.07.004. View

Rea I, Gibson D, McGilligan V, McNerlan S, Alexander H, Ross O . Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front Immunol. 2018; 9:586. PMC: 5900450. DOI: 10.3389/fimmu.2018.00586. View

Blank U, Karlsson S . TGF-β signaling in the control of hematopoietic stem cells. Blood. 2015; 125(23):3542-50. DOI: 10.1182/blood-2014-12-618090. View

Weinberger B . Vaccines for the elderly: current use and future challenges. Immun Ageing. 2018; 15:3. PMC: 5778733. DOI: 10.1186/s12979-017-0107-2. View

Bullone M, Lavoie J . The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma. Int J Mol Sci. 2017; 18(12). PMC: 5751215. DOI: 10.3390/ijms18122612. View

Abdel-Wahab N, Alshawa A, Suarez-Almazor M . Adverse Events in Cancer Immunotherapy. Adv Exp Med Biol. 2017; 995:155-174. DOI: 10.1007/978-3-319-53156-4_8. View

Sceneay J, Goreczny G, Wilson K, Morrow S, DeCristo M, Ubellacker J . Interferon Signaling Is Diminished with Age and Is Associated with Immune Checkpoint Blockade Efficacy in Triple-Negative Breast Cancer. Cancer Discov. 2019; 9(9):1208-1227. PMC: 11167954. DOI: 10.1158/2159-8290.CD-18-1454. View

Kovtonyuk L, Fritsch K, Feng X, Manz M, Takizawa H . Inflamm-Aging of Hematopoiesis, Hematopoietic Stem Cells, and the Bone Marrow Microenvironment. Front Immunol. 2016; 7:502. PMC: 5107568. DOI: 10.3389/fimmu.2016.00502. View

Pang W, Price E, Sahoo D, Beerman I, Maloney W, Rossi D . Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc Natl Acad Sci U S A. 2011; 108(50):20012-7. PMC: 3250139. DOI: 10.1073/pnas.1116110108. View

10.

Bruunsgaard H, Skinhoj P, Pedersen A, Schroll M, Pedersen B . Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis. Clin Exp Immunol. 2000; 121(2):255-60. PMC: 1905691. DOI: 10.1046/j.1365-2249.2000.01281.x. View

11.

Lee D, White D, Hurst R, Rosenberg S, Yang J . Patterns of relapse and response to retreatment in patients with metastatic melanoma or renal cell carcinoma who responded to interleukin-2-based immunotherapy. Cancer J Sci Am. 1998; 4(2):86-93. View

12.

Henry C, Casas-Selves M, Kim J, Zaberezhnyy V, Aghili L, Daniel A . Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors. J Clin Invest. 2015; 125(12):4666-80. PMC: 4665776. DOI: 10.1172/JCI83024. View

13.

Picca A, Lezza A, Leeuwenburgh C, Pesce V, Calvani R, Landi F . Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets. Int J Mol Sci. 2017; 18(5). PMC: 5454846. DOI: 10.3390/ijms18050933. View

14.

Fulop T, Larbi A, Kotb R, De Angelis F, Pawelec G . Aging, immunity, and cancer. Discov Med. 2011; 11(61):537-50. View

15.

Hutchins L, Unger J, Crowley J, COLTMAN Jr C, Albain K . Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999; 341(27):2061-7. DOI: 10.1056/NEJM199912303412706. View

16.

Herrera A, Snipes S, King D, Torres-Vigil I, Goldberg D, Weinberg A . Disparate inclusion of older adults in clinical trials: priorities and opportunities for policy and practice change. Am J Public Health. 2010; 100 Suppl 1:S105-12. PMC: 2837461. DOI: 10.2105/AJPH.2009.162982. View

17.

Santulli G, Borras C, Bousquet J, Calza L, Cano A, Illario M . Models for preclinical studies in aging-related disorders: One is not for all. Transl Med UniSa. 2016; 13:4-12. PMC: 4811343. View

18.

Xu X, Sun Q, Liang X, Chen Z, Zhang X, Zhou X . Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies. Front Immunol. 2019; 10:2664. PMC: 6863137. DOI: 10.3389/fimmu.2019.02664. View

19.

Yanez L, Sanchez-Escamilla M, Perales M . CAR T Cell Toxicity: Current Management and Future Directions. Hemasphere. 2019; 3(2):e186. PMC: 6746032. DOI: 10.1097/HS9.0000000000000186. View

20.

Duong L, Radley-Crabb H, Gardner J, Tomay F, Dye D, Grounds M . Macrophage Depletion in Elderly Mice Improves Response to Tumor Immunotherapy, Increases Anti-tumor T Cell Activity and Reduces Treatment-Induced Cachexia. Front Genet. 2018; 9:526. PMC: 6232269. DOI: 10.3389/fgene.2018.00526. View