Senescent Stromal Cells in the Tumor Microenvironment: Victims or Accomplices?

Simple Summary: Cellular senescence is a defensive response of cells to external stresses and occurs in a wide range of physiological and pathological processes, including neoplasms. Although tumor cell senescence may serve as a barrier to tumor proliferation, more studies have shown that stromal cell senescence in the tumor microenvironment contributes to the growth and regulation of tumor cells through senescence-associated secretory phenotypes. Herein, a review of the role of senescent stromal cells in the tumor microenvironment suggests that senescent stromal cells may be an accomplice in promoting tumor growth. This review contributes to understanding stromal cells in the tumor microenvironment and guides future research in the field. Cellular senescence is a unique cellular state. Senescent cells enter a non-proliferative phase, and the cell cycle is arrested. However, senescence is essentially an active cellular phenotype, with senescent cells affecting themselves and neighboring cells via autocrine and paracrine patterns. A growing body of research suggests that the dysregulation of senescent stromal cells in the microenvironment is tightly associated with the development of a variety of complex cancers. The role of senescent stromal cells in impacting the cancer cell and tumor microenvironment has also attracted the attention of researchers. In this review, we summarize the generation of senescent stromal cells in the tumor microenvironment and their specific biological functions. By concluding the signaling pathways and regulatory mechanisms by which senescent stromal cells promote tumor progression, distant metastasis, immune infiltration, and therapy resistance, this paper suggests that senescent stromal cells may serve as potential targets for drug therapy, thus providing new clues for future related research. [ABSTRACT FROM AUTHOR]