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TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune cells in head and neck squamous cell

Charlotte Leduc1,2,3,4,5,6, Julien Adam1,2, Emilie Louvet1

  • 1INSERM, UMR981, F-94805, Villejuif, France, Paris Sud University, Gustave Roussy, Villejuif, France.

ESMO Open
|January 19, 2018
PubMed
Abstract

Insights

Induction chemotherapy with docetaxel, platinum, and fluorouracil (TPF) significantly increases programmed cell death-ligand 1 (PD-L1) expression on immune cells and CD8+ T cells in advanced head and neck squamous cell carcinoma (HNSCC). This finding may inform future therapeutic strategies for HNSCC patients.

Area of Science:

  • Oncology
  • Immunotherapy
  • Head and Neck Cancer Research

Background:

  • Antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) therapies show promise in advanced head and neck squamous cell carcinoma (HNSCC).
  • The impact of induction docetaxel, platinum, and fluorouracil (TPF) chemotherapy on PD-L1 expression and tumor immune infiltrates in HNSCC is not well understood.

Purpose of the Study:

  • To evaluate the effect of induction TPF chemotherapy on PD-L1 expression in tumor cells (TC) and immune cells (IC).
  • To assess changes in CD8+ and Foxp3+ lymphocyte densities following TPF treatment in locally advanced HNSCC patients.

Main Methods:

  • Retrospective analysis of locally advanced HNSCC patients treated with induction TPF followed by surgery (2006-2013).
  • Quantification of PD-L1 expression (≥5% positivity threshold) on TC and IC using immunohistochemistry on paired pre-TPF and post-TPF samples.
  • Measurement of CD8+ and Foxp3+ lymphocyte densities before and after TPF induction chemotherapy.

Main Results:

  • A significant increase in PD-L1 positivity was observed in IC (71%) and TC (38%) after TPF induction chemotherapy (P=0.003 and P=0.005, respectively).
  • Tumor-infiltrating CD8+ lymphocyte densities significantly increased post-TPF (P=0.01).
  • No significant differences were found in Foxp3+ expression or the CD8/Foxp3 ratio, nor a correlation with outcome.

Conclusions:

  • Induction TPF chemotherapy demonstrably increases PD-L1 expression on tumor-infiltrating immune cells and enhances CD8+ lymphocyte density in advanced HNSCC.
  • These findings suggest TPF may modulate the tumor immune microenvironment, potentially impacting therapeutic strategies.
  • Further validation in larger cohorts is warranted to confirm these results and their clinical implications.
Keywords:
head and neck squamous cell carcinomaimmune checkpoint blockersimmunotherapyinduction chemotherapypd-l1

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