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Clinical Trial
. 2024 Apr;35(4):340-350.
doi: 10.1016/j.annonc.2023.12.011. Epub 2023 Dec 28.

B-cell infiltration is associated with survival outcomes following programmed cell death protein 1 inhibition in head and neck squamous cell carcinoma

N Gavrielatou  1 , E Fortis  2 , A Spathis  3 , M Anastasiou  4 , P Economopoulou  4 , G R P Foukas  3 , I M Lelegiannis  4 , S Rusakiewicz  2 , I Vathiotis  5 , T N Aung  5 , S Tissot  2 , A Kastrinou  4 , I Kotsantis  4 , E M Vagia  4 , I Panayiotides  3 , D L Rimm  5 , G Coukos  2 , K Homicsko  2 , P Foukas  3 , A Psyrri  6
Affiliations
Clinical Trial

B-cell infiltration is associated with survival outcomes following programmed cell death protein 1 inhibition in head and neck squamous cell carcinoma

N Gavrielatou et al. Ann Oncol. 2024 Apr.

Abstract

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). Programmed death-ligand 1 (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 were quantified by immunofluorescence using a five-protein panel (CD3, CD8, CD20, FoxP3, cytokeratin). Tertiary lymphoid structures (TLSs), 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) messenger RNA 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.

Keywords: B lymphocytes; head and neck neoplasms; immunotherapy; lymphocytes; programmed cell death 1 receptor; tumor infiltrating.

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Conflict of interest statement

Disclosure AP has served as an advisor for MSD, Nanobiotics, BMS, Astrazeneca, Merck Serono. She has received institutional research funding from BMS, Merck Serono, Roche, Sanofi. DLR has served as an advisor for Astra Zeneca, Agendia, Amgen, BMS, Cell Signaling Technology, Cepheid, Danaher, Daiichi Sankyo, Genoptix/Novartis, GSK, Konica Minolta, Merck, NanoString, PAIGE.AI, Perkin Elmer, Roche, Sanofi, and Ventana. Amgen, Cepheid, NavigateBP, NextCure, and Konica Minolta fund research in DLR’s lab. All other authors have declared no conflicts of interest.

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