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Journal Article
Review
Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.
Journal of Hematology & Oncology 2023 March 22
The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated secretory phenotype (SASP). On the one hand, the SASP promotes antitumor immunity, which enhances treatment efficacy; on the other hand, the SASP increases immunosuppressive cell infiltration, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and N2 neutrophils, contributing to TIME suppression. Therefore, a deeper understanding of the regulation of the SASP and components contributing to robust antitumor immunity in elderly individuals with different cancer types and the available therapies is necessary to control tumor cell senescence and provide greater clinical benefits to patients. In this review, we summarize the key biological functions mediated by cytokines and intercellular interactions and significant components of the TME landscape, which influence the immunotherapy response in geriatric oncology. Furthermore, we summarize recent advances in clinical practices targeting TME components and discuss potential senescent TME targets.
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