Table 3.

NSCLC immunotherapy efficacy prediction biomarkers.

Biomarkers	Details	Ref.
PD-L1 expression	NCCN-NSCLC guidelines have been recommended for PD-L1 testing from 2A to Category 1 since 2019. Using immunohistochemical methods, PD-L1 has ≥1% tumors in 60% of advanced NSCLC Cell expression, high level expression in 25–30% of patients (≥50% tumor cells).	[115,116]
TMB	NCCN-NSCLC expert group listed the TMB as a biomarker in the first edition of the 2019 NCCN guidelines. In 2020, TMB was approved by the FDA as a biomarker for pan-solid tumor immunotherapy.	[96]
TILs	TILs provide a promising treatment model for NSCLC patients with resistance after ICI treatment and confirm the value of TILs as predictive biomarkers, but its application value needs further exploration.	[104,105,106]
Driver gene mutations	Carrying EGFR mutations or ALK rearrangement is significantly correlated with the low response of NSCLC patients to ICIs. PIK3CA, EGFR, or STK11 mutations do not respond to ICIs, KRAS, TP53 mutants, and MET gene exon 14 skipping mutations respond well to ICIs.	[107,108,109,110]
Other biomarkers	The predictive value of microRNA, neoantigens, MSI, extracellular vesicles, gut metabolism, etc., for the efficacy of ICIs has also been widely studied, and some biomarkers perform well in predicting efficacy when used in combination.	[111,112,113]

Abbreviations: NSCLC, non-small cell lung cancer; NCCN, National Comprehensive Cancer Network; PD-1, programmed cell death receptor-1; PD-L1, programmed cell death ligand 1; TMB, tumor mutation burden; FDA, Food and Drug Administration; TILs, tumor-infiltrating lymphocytes; ICI, immune checkpoint inhibitor; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; MET, mesenchymal-to-epithelial transition factor; MSI, microsatellite instability.