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Abstract The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases of the disease and progress under intense evolutionary pressures. Organ-specific metastasis relies on the formation of pre-metastatic niche (PMN), with diverse cell types and complex cell interactions contributing to this concept, adding a new dimension to the traditional metastasis cascade. Prior to metastatic dissemination, as orchestrators of PMN formation, primary tumor-derived extracellular vesicles prepare a fertile microenvironment for the settlement and colonization of circulating tumor cells at distant secondary sites, significantly impacting cancer progression and outcomes. Obviously, solely intervening in cancer metastatic sites passively after macrometastasis is often insufficient. Early prediction of metastasis and holistic, macro-level control represent the future directions in cancer therapy. This review emphasizes the dynamic and intricate systematic alterations that occur as cancer progresses, illustrates the immunological landscape of organ-specific PMN creation, and deepens understanding of treatment modalities pertinent to metastasis, thereby identifying some prognostic and predictive biomarkers favorable to early predict the occurrence of metastasis and design appropriate treatment combinations.

Abstract Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed “immunosenescence,” which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underlying immunosenescence, detailing alterations in immunosenescence at molecular, cellular, organ, and disease levels. The role of immunosenescence in tumorigenesis and senescence‐related extracellular matrix (ECM) has also been addressed. Recognizing that immunosenescence is a dynamic process influenced by various factors, we will evaluate treatment strategies targeting hallmarks and molecular mechanisms, as well as methods for immune cell, organ restoration, and present emerging approaches in immunosenescence for tumor immunotherapy. The overarching goal of immunosenescence research is to prevent tumor development, recurrence, and metastasis, ultimately improving patient prognosis. Our review aims to reveal latest advancements and prospective directions in the field of immunosenescence research, offering a theoretical basis for development of practical anti‐immunosenescence and anti‐tumor strategies.