CELL INTELLIGENCE · 肿瘤细胞治疗研究

Immune evasion in cancer is frequently mediated by checkpoint molecules such as programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), which suppress T-cell recognition and perpetuate tumor progression. To counter this immunosuppressive axis, immune checkpoint inhibitors (ICIs) have been developed to reinvigorate antitumor immunity by reversing T lymphocyte dysfunction. Over 30 ICIs have been clinically approved for the treatment of malignant tumors. Despite these advances, ICI monotherapy remains limited due to the primary or acquired resistance and suboptimal efficacy in immunologically "cold" tumor microenvironments characterized by inadequate T-cell infiltration. To address these challenges, combinatorial strategies integrating ICIs with tumor-infiltrating lymphocyte (TIL) therapy are gaining momentum. This review synthesizes preclinical and clinical evidences supporting TIL-ICI synergy in solid tumors, wherein adoptively transferred tumor-reactive T cells enhance intratumoral immune activation while ICIs sustain TIL effector functions by alleviating checkpoint constraints. We further discuss emerging strategies to optimize this paradigm, including engineered TILs with enhanced persistence, biomarker-driven patient stratification, and multimodal regimens incorporating anti-angiogenics or epigenetic modulators. Despite promising early-phase trial outcomes, barriers to clinical adoption still persist, such as manufacturing complexity, immune-related toxicity management, and the paucity of Phase III validation. By delineating mechanistic rationale, current progress, and translational roadblocks, this work provides a roadmap for advancing TIL-ICI combinations toward broader therapeutic implementation.