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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Therapeutic Targeting of MYC in Head and Neck Squamous Cell Carcinoma

Shuo Liu1,2, Zhen Qin1,2,3, Yaqing Mao1,2

  • 1Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.

Oncoimmunology
|October 10, 2022
PubMed

Insights

MYC inhibitors effectively reduce head and neck squamous cell carcinoma (HNSCC) growth and migration. MYC inhibition also enhances anti-tumor immunity by promoting CD8+ T cell infiltration, suggesting potential as a cancer therapy.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • MYC is a critical driver of tumorigenesis and a promising cancer therapeutic target.
  • Small molecule MYC inhibitors offer potential as well-tolerated anti-cancer agents.
  • Head and neck squamous cell carcinoma (HNSCC) presents a significant clinical challenge.

Purpose of the Study:

  • To investigate the therapeutic efficacy of MYC inhibitors in HNSCC.
  • To explore the impact of MYC inhibition on HNSCC growth, migration, and immune responses.

Main Methods:

  • Pharmacological and genetic inhibition of MYC.
  • Assessment of HNSCC proliferation and migration in vitro.
  • Evaluation of MYC inhibitor 975 (MYCi975) in xenograft and syngeneic murine models.
  • Analysis of tumor cell-intrinsic immune responses and CD8+ T cell infiltration.
  • Investigation of the cGAS-STING pathway in response to MYC inhibition.

Main Results:

  • MYC inhibition significantly suppressed HNSCC proliferation and migration.
  • MYCi975 demonstrated efficacy in reducing HNSCC tumor growth in preclinical models.
  • MYC inhibition promoted CD8+ T cell infiltration and induced tumor cell-intrinsic immune responses.
  • MYC inhibition activated the cGAS-STING pathway, increasing chemokine production.
  • High MYC expression with low CD8+ T cell infiltration correlated with poor HNSCC prognosis.

Conclusions:

  • Small-molecule MYC inhibitors show significant therapeutic potential for HNSCC.
  • MYC inhibition enhances anti-tumor immunity, making it a viable strategy for HNSCC treatment.
  • Targeting MYC may overcome immune evasion in HNSCC and improve patient outcomes.
Keywords:
CD8+ T cellDNA damage responseMYCMYCi975cGAS-STINGhead and neck squamous cell carcinoma

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