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Biomarker Analysis Evaluates Potential for Immune Checkpoint Blockade Response in Older Patients With Cancer


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A retrospective analysis of large data sets of biomarkers from tumors and healthy tissue by researchers at the Johns Hopkins Kimmel Cancer Center Convergence Institute suggests that older patients with cancer may benefit as much from cancer immunotherapies as younger patients. The findings, published recently by Erbe et al in Cell Reports, provide support for potentially expanding the use of these agents in the elderly, a population in which immunotherapies may be underprescribed.

“The interaction between age, immunity, and cancers has been understudied, particularly with the rise of cancer immunotherapies,” said first study author Rossin Erbe, a PhD candidate at the Johns Hopkins University School of Medicine and a member of the laboratory of study co-leader Elana Fertig, PhD, Associate Professor of Oncology. 

Researchers have long known that cancer incidence increases exponentially as people age, with more than two-thirds of all new cancers diagnosed in patients older than 60 years, according to data from the Centers for Disease Control and Prevention. Concurrently, aging also lowers general immunity, with older patients being 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, these immunotherapies are less commonly prescribed to the elderly as a result of their dampened general immunity, explained Dr. Erbe. Yet, some clinical trials have suggested that elderly patients with cancer have just as good or better responses to immunotherapies.

KEY POINTS

  • 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 and a greater population of immune-suppressing macrophages, specifically in some breast cancers.

Current Analysis

To resolve this discrepancy and better understand how patient age might affect response to immunotherapy, the research team collected genomics 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 patients with cancer with 31 different types of malignancies.

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, expression of immune checkpoint proteins, expression of inflammation-related pathways (such as interferon gamma), and 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 and a greater population of immune-suppressing macrophages, specifically in some breast cancers.

Overall, these data suggest that biomarkers for immunotherapies could still be used as a basis to select immunotherapy treatment in older patients as in young ones, said Dr. Fertig, who is also Co-Director of the Convergence Institute and Director of Quantitative Sciences. This idea was supported by clinical findings in two other databases used in this study: one that tracked patients with renal cell carcinoma, and another that tracked U.S. Veterans Administration patients.

However, she added, a variety of factors beyond these biomarkers must be considered when prescribing immunotherapies to older patients, such as frailty and other health conditions that could affect patients’ response and ability to manage side effects.

“Characteristics of tumors from older patients certainly have biological properties consistent with a robust immune response,” Dr. Fertig concluded. “We think this is something that deserves more study using tumor atlases with prospective study designs that are tailored to study aging and immunotherapy response.”

Disclosure: This research was supported by the National Institutes of Health, the National Cancer Institute, the Lustgarten Foundation, and the Grollman Glick Scholar Award. For full disclosures of the study authors, visit cell.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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