- D3.546 - AllergoOncology: Basophil number and subpopulation proportions may offer potential as predictive biomarkers in non-small cell lung cancer

Basophils have emerged as potential modulators of tumor immunity. Recent evidence suggests that their presence, frequency, and activation profile in peripheral blood and tumor microenvironment are associated with clinical outcomes and may serve as prognostic biomarkers. Although distinct basophil subpopulations have recently been described, their relative proportions and clinical relevance in cancer remain poorly understood.

This study aimed to analyse basophil numbers and subpopulations in non-small cell lung cancer (NSCLC) patients and to explore associations with patient clinical outcome following immune checkpoint inhibitor (ICI) therapy.

Basophils were characterized by flow cytometry in whole blood from 27 patients with stage IV NSCLC receiving ICI and 14 healthy volunteers (HV) using HLA-DR, CD123, CD16, FcεRI, and CD244. Patients were classified according to clinical outcome as typical course (n=15), hyperprogression (n=3), long-responders (n=5), and immune-related adverse events (irAEs) (n=4). 

At baseline, patients with a typical clinical course displayed a significantly lower circulating basophil percentage compared with HV (0.18% vs 0.61%; p=0.001), despite similar distributions of CD16^low (92.5% vs 92.8%) and CD16^high (7.5% vs 7.2%). In contrast, these patients exhibited a significantly higher proportion of FcεRI^lowCD244^high basophils (0.49% vs 0.25%; p=0.002).

Baseline blood samples, for patients who experienced rapid tumor growth after ICI, and died within 12 days (hyperprogression), had lower percentage of basophils than HV (0.034% vs 0.61%; p=0.04), but similar to typical course patients.

Blood samples from long-response patients, who were in remission with median of 34 months from treatment initiation, had a basophil percentage (0.55%) and subpopulation distribution were similar to HV.

Likewise, four patients developed grade 2 irAEs after a median of 6.5 months (range: 6–14) of treatment initiation. Basophil percentage in baseline samples from these patients was similar to HV (0.59%), and they exhibited a significantly higher proportion of FcεRI^highCD244^high basophils compared with typical patients (99.1% vs 98.2%; p=0.04).

Circulating basophil frequency and subpopulation profiles differ according to clinical course in grade IV NSCLC patients receiving ICI. The distinct patterns observed among the different groups supports a potential role of basophils as candidate predictive biomarkers, warranting validation in larger prospective studies.