Nanomedicine holds promise for improving treatment and prognosis in elderly cancer patients by targeting immunosenescence

Immunosenescence, a key hallmark of aging, is closely linked to increased cancer incidence and diminished immunotherapy efficacy among the elderly population. Despite groundbreaking advances in cancer immunotherapy, there is a significant disparity in treatment outcomes and prognosis between younger and older cancer patients. Clinical studies indicate that elderly patients with non-small cell lung cancer derive minimal survival benefits from immunotherapy compared to their younger counterparts. Given the global aging population and the rising cancer burden, this disparity demands urgent attention. The team led by Professor Kai Miao from the University of Macau has systematically reviewed the potential of nanomedicine to address this challenge, offering innovative strategies to enhance immunotherapy in elderly patients.

This review, published in the journal Nano Research, emphasizes how immunosenescence disrupts the homeostasis of both innate and adaptive immunity, thereby fostering a microenvironment permissive to tumorigenesis. Key issues include thymic involution, hematopoietic stem cell dysregulation, and chronic inflammation, all of which collectively impair anti-tumor responses. Meanwhile, because most preclinical models overlook age-related immune decline, conventional therapies often fall short in elderly patients, who account for over 50% of global cancer cases.

Nanomedicine combines nanotechnology and medicine, leveraging advanced nanomaterials and targeted drug delivery techniques with tumor immunotherapy to enhance its efficacy and prognosis in elderly cancer patients. Building on this, Professor Kai Miao's team has comprehensively summarized that nanomedicines can specifically target and ameliorate immunosenescence within the TME through three complementary mechanisms: remodeling the immunosuppressive TME, targeting accumulated senescent cells, and mimicking functional immune cells. These strategies have the potential to transform treatment paradigms for elderly cancer patients who currently derive limited benefits from standard immunotherapies.

"In this review, we have, for the first time, comprehensively integrated three rapidly evolving fields: immunosenescence, tumor microenvironment biology, and nanomedicine," says Professor Kai Miao. "We systematically delineate the bidirectional regulatory relationship between immunosenescence and the TME, establishing a novel conceptual framework to explain why elderly cancer patients often respond poorly to immunotherapy. This synthetic approach significantly advances existing literature, which typically addresses these fields in isolation. Furthermore, our review offers several key scientific insights:

1. Immunosenescence is not merely a passive bystander during carcinogenesis but actively promotes tumorigenesis through specific molecular mechanisms, creating a self-reinforcing cycle.

2. We provide compelling evidence that nanomedicine, through its precision targeting and multifunctional design, offers unique capabilities unachievable by conventional therapies to overcome immunosenescence-related hurdles.

3. We synthesize emerging evidence suggesting that age-related changes in liver macrophages can actually enhance the accumulation of nanodrugs in tumors in the elderly, revealing an unexpected therapeutic opportunity."

This work was supported by multiyear research grant (MYRG) MYRG-GRG2023-00150-FHS-UMDF and MYRG-GRG2024-00146-FHS to K. M. by the University of Macau, Macau SAR, China

About the Authors

Kai Miao is a Professor and Ph.D. supervisor at the University of Macau, President of the Macau Young Scientists Association, and a member of the Academic Committee of the World Young Scientist Summit. His primary research interests are in functional genomics, including: (1) high-throughput functional gene screening and identification based on single-cell barcode-labeled CRISPR libraries; (2) functional characterization of tumor DNA methylation drivers; and (3) lineage tracing analysis of tumor metastasis. He leads or participates in multiple research projects, including Key Programs of the National Natural Science Foundation of China, Macao Science and Technology Development Fund Key R&D Special Projects, and University of Macau Research Grants. In recent years, he has published over 70 SCI papers in international journals such as Nature Cell Biology, Nature Communications, Cell Research, Advanced Science, PNAS, and Oncogene.

About Nano Research

Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.