Both tumors and aging alter the immune landscape of tissues. However, the interplay between these processes in the immune tumor microenvironment (ITME) is largely unknown. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care, particularly for immunotherapies. We leverage large scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased Interferon Gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy. Concurrently, we observe age-related alterations that might be expected to reduce ICB efficacy, such as increases in macrophage abundance and decreases in T cell receptor diversity. Altogether, these changes point to sustained activation of pathways associated with ICB response in many older patients and the need for increasing cognizance of ITME characterization when considering the impact of age on selection for ICB treatment.
We additionally perform general analyses of the relationship of age and molecular and cellular markers within cancer types with the intent of providing a broad overview of the relationship between age and cancer, which we make available as the Cancer Associations with Molecular Aging (CAMA) Atlas: http://www.lab-apps.onc.jhmi.edu/CAMAAtlas.