Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy

ABSTRACT: The tumor immune microenvironment (TIME) plays a pivotal role in tumor initiation, progression, and therapeutic response, and is closely associated with long-term treatment efficacy. Notably, therapeutic interventions are not only influenced by the immune microenvironment but also actively remodel its cellular and molecular architecture. In recent years, advanced technologies such as single-cell sequencing, spatial transcriptomics, and other multi-omics approaches have provided unprecedented insights into the dynamic interplay between therapeutic modalities and the TIME, as well as the secondary microenvironmental changes that critically influence immunotherapy outcomes. In this review, we summarize therapy-induced remodeling of the TIME, elucidate the mechanisms by which these changes modulate immunotherapy responsiveness, and discuss potential strategies for therapeutic optimization. A deeper understanding of therapy-driven alterations in the TIME, empowered by emerging high-resolution technologies, will not only facilitate the monitoring and prediction of treatment efficacy but also guide the development of more precise and individualized combination treatment strategies.