Table 1.

Framework summarizing the evolving PD-L1 evidence layers in non-small cell lung cancer (NSCLC) immunotherapy

Analytical Layer	Key Insight	Interaction With PD-L1	Translational Relevance	Evidence Type	References
Mutational Burden & Neoantigens	Transition from total mutation counts to neoantigen quality	Interferon signaling may couple mutation load with inducible PD-L1	Guides patient stratification+vaccine/ICI combinations	Clinical+Computational	(51)
Tumor Microenvironment	Spatial immune niches define checkpoint expression	PD-L1 enriched in immune–stromal interfaces	Enables biopsy targeting+radiomic mapping	Clinical	(52)
Circulating / Liquid Biomarkers	Noninvasive PD-L1 and immune signatures emerging	Exosomal PD-L1 contributes to systemic immune suppression	Supports longitudinal monitoring and adaptive dosing	Emerging clinical	(33)
Temporal Dynamics	PD-L1 is fluctuating rather than static	IFN-γ and therapy pressure induce oscillatory regulation	Supports dynamic biomarker frameworks	Translational	(53)
AI-Driven Predictors	Multimodal models integrate genomics, imaging, and immune profiling	Learns causal immuno-regulatory networks	Enables digital-twin–based personalization	Computational	(12)