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

B-Lymphocytes Head and Neck Neoplasms Immunotherapy Lymphocytes Programmed Cell Death 1 Receptor Tumor-Infiltrating

Journal

Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735

Informations de publication

Date de publication:
28 Dec 2023
Historique:
received: 06 11 2023
revised: 12 12 2023
accepted: 19 12 2023
medline: 2 1 2024
pubmed: 2 1 2024
entrez: 30 12 2023
Statut: aheadofprint

Résumé

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. 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. 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). 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

DOI: 10.1016/j.annonc.2023.12.011 PMID: 38159908
pubmed: 38159908
pii: S0923-7534(23)05118-9
doi: 10.1016/j.annonc.2023.12.011
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023. Published by Elsevier Ltd.

Auteurs

N Gavrielatou (N)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece;; Yale University School of Medicine, Department of Pathology, USA.

E Fortis (E)

Ludwig Institute for Cancer Research, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

A Spathis (A)

Departments of Pathology Attikon University Hospital, National Kapodistrian University of Athens, Haidari, Athens, Greece.

M Anastasiou (M)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece.

P Economopoulou (P)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece.

G R P Foukas (GRP)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece.

I M Lelegiannis (IM)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece.

S Rusakiewicz (S)

Ludwig Institute for Cancer Research, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

I Vathiotis (I)

Yale University School of Medicine, Department of Pathology, USA.

T N Aung (TN)

Yale University School of Medicine, Department of Pathology, USA.

S Tissot (S)

Ludwig Institute for Cancer Research, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

A Kastrinou (A)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece.

I Kotsantis (I)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece.

E M Vagia (EM)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece.

I Panayiotides (I)

Departments of Pathology Attikon University Hospital, National Kapodistrian University of Athens, Haidari, Athens, Greece.

D L Rimm (DL)

Yale University School of Medicine, Department of Pathology, USA.

G Coukos (G)

Ludwig Institute for Cancer Research, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

K Homicsko (K)

Ludwig Institute for Cancer Research, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

P Foukas (P)

Departments of Pathology Attikon University Hospital, National Kapodistrian University of Athens, Haidari, Athens, Greece.

A Psyrri (A)

Departments of Internal Medicine (Section of Medical Oncology), National Kapodistrian University of Athens, Haidari, Athens, Greece;. Electronic address: dpsyrri@med.uoa.gr.

Classifications MeSH