The next decade will transition from broad TME disruption to precision engineering. AI-driven spatial omics will refine biomarker-led selection, identifying 'TME phenotypes' for tailored therapy. Emerging multi-immune-axis platforms, such as immunostimulatory antibody conjugates (ISACs) and bispecific ADCs, will transcend single-target limitations. We anticipate regulatory approvals of TME-targeted ADCs for 'cold' tumors within five years, serving as priming agents for immunotherapy. Within ten years, TME-targeted ADCs should migrate to neoadjuvant settings to 'normalize' the tumor ecosystem before surgery. This evolution from treatment in advanced settings to foundational curative therapy, using personalized ADC combinations tailored to individual immune landscapes, will be essential to overcome adaptive resistance and achieve long-term remission.
Xu et al. (Sun,) studied this question.