Peripheral blood biomarkers associated with combination of immune checkpoint blockade plus chemotherapy in NSCLC

BACKGROUNDBiomarkers predicting clinical outcomes of treating non-small cell lung cancer (NSCLC) with combination of immune checkpoint inhibitors (ICIs) and chemotherapy would be valuable.OBJECTIVEThis study aims to seek predictors of combination of ICI/chemotherapy response in NSCLC patients using peripheral blood samples.METHODSPatients diagnosed with advanced NSCLC between July 2019 and May 2021 receiving combination of ICI/chemotherapy were included and assessed for partial responses (PR), stable disease (SD) or progressive disease (PD). We measured circulating immune cells, plasma cytokines and chemokines.RESULTSNineteen patients were enrolled. The proportions of circulating natural killer (NK) cells within CD45⁺ cells, programmed death 1 (PD-1)⁺ Tim-3⁺ T cells within CD4⁺ cells, and the amount of chemokine C-X-C ligand (CXCL10) in the plasma were significantly elevated in PR relative to SD/PD patients (median 8.1%-vs-2.1%, $P=$ 0.0032; median 1.2%-vs-0.3%, $P=$ 0.0050; and median 122.6 pg/ml-vs-76.0 pg/ml, $P=$ 0.0125, respectively). Patients with 2 or 3 elevated factors had longer progression-free survival than patients with 0 or only one (not reached-vs-5.6 months, $P=$ 0.0002).CONCLUSIONSWe conclude that NK cells, CD4⁺ PD-1⁺ Tim-3⁺ T cells, and CXCL10 levels in pre-treatment peripheral blood may predict the efficacy of combination of ICI/chemotherapy in NSCLC.