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Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders

Liye Zhou1, Zexian Zeng2, Ann Marie Egloff3

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Journal for Immunotherapy of Cancer
|January 21, 2022
PubMed
Abstract

Insights

Immune checkpoint blockade (ICB) resistance in head and neck squamous cell carcinoma (HNSCC) involves distinct tumor microenvironments and T cell dynamics. Enhancing CD8+ T cell differentiation may improve ICB response in HNSCC patients.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Immune checkpoint blockade (ICB) shows limited efficacy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), with resistance mechanisms poorly understood.
  • Understanding the tumor microenvironment and immune cell dynamics is crucial for improving ICB response rates in HNSCC.

Purpose of the Study:

  • To investigate the mechanisms of anti-PD1 resistance in HNSCC.
  • To characterize the tumor microenvironment and T cell heterogeneity in sensitive versus resistant HNSCC models.
  • To identify potential strategies for enhancing ICB efficacy in HNSCC.

Main Methods:

  • Generation of an isogenic anti-PD1 resistant murine HNSCC model (MOC1esc1) from a sensitive parental line (MOC1).
  • Mass cytometry to profile tumor microenvironments of sensitive and resistant tumors.
  • Paired single-cell RNA and TCR sequencing to analyze tumor-infiltrating lymphocyte (TIL) heterogeneity and dynamics in three HNSCC models.

Main Results:

  • The anti-PD1 resistant MOC1esc1 line exhibited an intrinsic immune evasion signature.
  • Distinct baseline tumor microenvironments and immune compartment remodeling upon ICB were observed in resistant vs. sensitive models.
  • Single-cell analysis identified distinct CD8+ TIL subsets (naïve/memory-like, progenitor, differentiated effector) and revealed that effective ICB therapy promotes T cell lineage transitions.

Conclusions:

  • CD8+ T cell heterogeneity and differentiation are critical factors in HNSCC ICB response.
  • Facilitating CD8+ T cell differentiation presents a promising strategy to enhance ICB efficacy in HNSCC.
Keywords:
head and neck neoplasmslymphocytestumor microenvironmenttumor-infiltrating

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