Older patients benefit from cancer immunotherapies

Sept. 8, 2021

A retrospective analysis of large datasets of biomarkers from tumors and healthy tissue by researchers at the Johns Hopkins Kimmel Cancer Center Convergence Institute suggests that older cancer patients could benefit as much as younger patients from cancer immunotherapies.

The findings, published online in Cell Reports, provide support for potentially expanding the use of these promising therapies in the elderly, a population in which immunotherapies may be under prescribed.

“The interaction between age, immunity, and cancers has been understudied, particularly with the rise of cancer immunotherapies,” says Rossin Erbe, PhD Candidate at the Johns Hopkins University School of Medicine.

Researchers have long known that cancer incidence increases exponentially as people age, with more than two-thirds of all new cancers diagnosed in patients more than 60 years old, according to the Centers for Disease Control and Prevention (CDC). Concurrently, aging also lowers general immunity, with older patients less able to mount an effective immune response to disease.

Although a variety of medicines that stimulate the body’s immune system to fight cancer have been approved in recent years, says Erbe, these immunotherapies are less commonly prescribed to the elderly as a result of their dampened general immunity. Yet, some clinical trials have suggested that elderly cancer patients have just as good or better responses to immunotherapies.

To resolve this discrepancy and better understand how a patient's age might affect immunotherapy success, researchers collected genomic and clinical data obtained from tumors and healthy tissues stored in several databases, including: the Cancer Genome Atlas; the Genomics Evidence Neoplasia Information Exchange; a database run by Caris Life Sciences; the Molecular Taxonomy of Breast Cancer, and the Genotype-Tissue Expression project. These databases encompassed a total of 77,732 cancer patients with 31 different cancer types.

Using this wealth of information, the researchers developed a publicly accessible web application called Cancer Associations with Molecular Aging (CAMA) to compare various factors across patients of varying ages in healthy and malignant tissue. Factors included mutational burden (the number of genetic mutations the cancer contained), expression of immune checkpoint proteins — the signals that initiate and stop immune responses — that many cancer immunotherapies act on, the expression of inflammation-related pathways, such as interferon gamma, and the cell composition of cells in and around tumors, known as the tumor microenvironments.

Their analysis showed that aging is associated with a variety of factors known to correlate with increased response to immunotherapies, such as an uptick in the number of mutations in tumor cells, increased expression of immune checkpoint proteins, and increased interferon gamma signaling. However, age is also associated with factors that could decrease immune response, including a lack of diversity of T cell receptors (proteins that allow immune cells to recognize and kill cancer cells), and a greater population of immune suppressing cells known as macrophages, specifically in some breast cancers.

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