B-cell infiltration is associated with survival outcomes following programmed cell death protein 1 inhibition in head and neck squamous cell carcinoma
Menée à partir d'échantillons biopsiques et d'échantillons sanguins prélevés sur 60 patients traités par anti-PD1 pour un carcinome épidermoïde de la tête et du cou récidivant et/ou métastatique, cette étude met en évidence une association entre la concentration de lymphocytes B dans le stroma tumoral avant traitement et la survie des patients
Background : Programmed cell death protein 1(PD-1) axis blockade has become the mainstay in the treatment of recurrent and/or metastatic (R/M) head and neck squamous cell cancer (HNSCC). PD-L1 is the only approved biomarker for patient selection; however, response rate is limited even among high expressors. Our primary objective was to investigate the association of immune-cell-related biomarkers in the tumor and tumor microenvironment with PD-1 checkpoint inhibitors' outcomes in patients with R/M HNSCC.
Patients and methods : NCT03652142 was a prospective study in nivolumab-treated platinum-refractory R/M HNSCC, aiming to evaluate biomarkers of response to treatment. Tumor biopsies and blood samples were collected from 60 patients at baseline, post-treatment, and at progression. Immune cells in the tumor and stromal compartments was quantified by immunofluorescence using a five-protein panel (CD3, CD8, CD20, Foxp3, Cytokeratin). Tertiary lymphoid structures (TLS), PD-L1 expression, and peripheral blood immune-cell composition were also evaluated for associations with outcome. Our findings were validated by gene set enrichment analysis (GSEA) mRNA in situ expression data from the same patients, for B-cell and TLS associated genes.
Results : High pre-treatment density of stromal B-cells was associated with prolonged progression-free survival (PFS) (p=0.011). This result was validated by GSEA, as stromal enrichment with B-cell-associated genes showed association with response to nivolumab. PD-L1 positivity combined with high B-cell counts in stroma defined a subgroup with significantly longer PFS and overall survival (p=0.013 and p=0.0028, respectively).
Conclusions : Increased B-cells in pre-treatment HNSCC biopsy samples correlate with prolonged benefit from PD-1-based immunotherapy and could further enhance the predictive value of PD-L1 expression.
Annals of Oncology , article en libre accès, 2022