Current advances and future directions of combined ICIs and TILs in solid tumors

Area of Science:

• Oncology
• Immunology
• Cancer Therapy

Background:

• Immune evasion in cancer is often driven by checkpoint molecules like PD-1, PD-L1, and CTLA-4, which inhibit T-cell responses and promote tumor growth.
• Immune checkpoint inhibitors (ICIs) have been developed to restore antitumor immunity, with over 30 approved for treating various cancers.
• However, ICI monotherapy faces limitations due to resistance and poor efficacy in 'cold' tumors lacking T-cell infiltration.

Purpose of the Study:

• To review preclinical and clinical evidence supporting the synergistic combination of ICIs and tumor-infiltrating lymphocyte (TIL) therapy in solid tumors.
• To explore emerging strategies for optimizing TIL-ICI combinations, including engineered TILs, biomarker-based patient selection, and multimodal treatments.
• To identify barriers to clinical adoption and provide a roadmap for advancing TIL-ICI combinations.

Main Methods:

• Synthesis of preclinical and clinical data on TIL-ICI combinations in solid tumors.
• Discussion of mechanistic rationale for TIL-ICI synergy.
• Analysis of ongoing research, emerging strategies, and translational challenges.

Main Results:

• Adoptively transferred tumor-reactive T cells (TILs) enhance intratumoral immune activation.
• ICIs sustain TIL effector functions by overcoming checkpoint-mediated suppression.
• Emerging strategies like engineered TILs and multimodal regimens show potential for improved outcomes.

Conclusions:

• TIL-ICI combination therapy offers a promising strategy to enhance antitumor immunity and overcome resistance to ICI monotherapy.
• Further research and clinical validation are needed to address manufacturing complexity, toxicity, and establish efficacy in large trials.
• Optimizing TIL-ICI combinations through advanced engineering and patient stratification is crucial for broader therapeutic application.