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TAF1 Suppresses MHC-I Expression and Correlates with Poor Immunotherapy Response in Small Cell Lung Cancer

Qing Gao1,2, Kehong Wei2, Deshen Pan2

  • 1Department of Radiation Oncology, Institute of Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Biomedicines
|May 27, 2026
PubMed

Insights

Small cell lung cancer (SCLC) is resistant to immunotherapy. Researchers found the epigenetic regulator TAF1 suppresses immune response by reducing MHC-I expression, suggesting TAF1 as a therapeutic target to improve SCLC immunotherapy outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Epigenetics
  • Cancer Genomics

Background:

  • Small cell lung cancer (SCLC) exhibits intrinsic resistance to immunotherapy due to its low immunogenicity and immune-cold tumor microenvironment.
  • The underlying mechanisms contributing to SCLC's immunotherapy resistance are not well understood.
  • Identifying novel therapeutic targets is crucial for enhancing treatment efficacy in SCLC.

Purpose of the Study:

  • To systematically screen epigenetic regulators for their association with CD8+ T cell infiltration and clinical outcomes in SCLC.
  • To identify potential therapeutic targets for overcoming immunotherapy resistance in SCLC.
  • To investigate the functional role of candidate epigenetic regulators in SCLC's immune microenvironment.

Main Methods:

  • Systematic screening of 796 epigenetic regulators in SCLC.
  • Integration of multi-omics SCLC datasets, including scRNA-seq, bulk RNA-seq (IMpower133 cohort), and proteomic data.
  • In vitro and in vivo functional experiments to validate candidate gene roles.

Main Results:

  • The epigenetic regulator TAF1 was identified as a key candidate, negatively correlating with CD8+ T cell infiltration in SCLC.
  • Low TAF1 expression correlated with improved outcomes in SCLC patients treated with atezolizumab-based chemoimmunotherapy, especially in ASCL1-high tumors.
  • TAF1 expression inversely correlated with MHC-I expression; TAF1 knockdown restored MHC-I, suppressed tumor growth, and increased CD8+ T cell infiltration in vivo.

Conclusions:

  • TAF1 acts as an epigenetic suppressor of MHC-I expression in SCLC.
  • Targeting TAF1 presents a potential therapeutic strategy to enhance immunotherapy efficacy in SCLC.
  • Further investigation into TAF1 inhibition could lead to novel treatment approaches for SCLC patients.
Keywords:
TAF1antigen presentationepigenetic regulatorimmunotherapysmall cell lung cancer

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