# Research progress on the spatiotemporal dynamics of therapy-induced senescence in remodeling the tumor microenvironment

## TL;DR

This review explores how therapy-induced senescence changes the tumor environment over time and space, with both helpful and harmful effects.

## Contribution

The paper highlights the spatiotemporal dynamics and dual role of TIS in the TME, offering new insights into its tumor-suppressive and tumor-promoting functions.

## Key findings

- TIS influences the TME through SASP, affecting fibroblasts, vasculature, and immune responses.
- The dual effect of TIS varies by treatment stage and location, with a threshold between tumor suppression and promotion.
- Future strategies include multi-omics monitoring and AI to better target the senescent microenvironment.

## Abstract

This review systematically elaborates on the spatiotemporal dynamics and dual role of Therapy-Induced Senescence (TIS) in remodeling the Tumor Microenvironment (TME). The hallmark of TIS is the Senescence-Associated Secretory Phenotype (SASP), which drives multidimensional TME reprogramming through the secretion of various factors. These effects include the activation of Cancer-Associated Fibroblasts (CAFs), promotion of Vasculogenic Mimicry (VM), induction of metabolic reprogramming, and bidirectional regulation of the immune landscape. The article provides a focused analysis of the heterogeneous manifestations of this dual effect across different treatment stage and spatial locations, highlighting the definition of the threshold between its tumor-suppressive and tumor-promoting functions as a central current challenge. Finally, it explores future strategies involving multi-omics dynamic monitoring, artificial intelligence analysis, and spatiotemporally specific targeted interventions. In summary, this review aims to provide a theoretical foundation and translational directions for developing novel combination therapies targeting the senescent microenvironment by offering an in-depth analysis of the spatiotemporal dynamics of TIS.