Pan-cancer transcriptomic analysis identified six classes of immunosenescence genes revealed molecular links between aging, immune system and cancer.

Aging is a complex process that significantly impacts the immune system. The aging-related decline of the immune system, termed immunosenescence, can lead to disease development, including cancer. The perturbation of immunosenescence genes may characterize the associations between cancer and aging. However, the systematical characterization of immunosenescence genes in pan-cancer remains largely unexplored. In this study, we comprehensively investigated the expression of immunosenescence genes and their roles in 26 types of cancer. We developed an integrated computational pipeline to identify and characterize immunosenescence genes in cancer based on the expression profiles of immune genes and clinical information of patients. We identified 2218 immunosenescence genes that were significantly dysregulated in a wide variety of cancers. These immunosenescence genes were divided into six categories based on their relationships with aging. Besides, we assessed the importance of immunosenescence genes in clinical prognosis and identified 1327 genes serving as prognostic markers in cancers. BTN3A1, BTN3A2, CTSD, CYTIP, HIF1AN, and RASGRP1 were associated with ICB immunotherapy response and served as prognostic factors after ICB immunotherapy in melanoma. Collectively, our results furthered the understanding of the relationship between immunosenescence and cancer and provided insights into immunotherapy for patients.