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Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
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FAM135B Deficiency Inhibits Cytotoxic T-cell Activity in Triple-Negative Breast Cancer by Blocking the

Wanmei Lin1,2, Junze Li1,2, Jun Wu2,3

  • 1Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Cancer Immunology Research
|November 11, 2025
PubMed

Insights

Sequence similarity 135 family member B (FAM135B) activates cytotoxic T cells via the STING pathway, enhancing immune checkpoint blockade efficacy in triple-negative breast cancer (TNBC). FAM135B may predict treatment response in TNBC patients.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Immune checkpoint blockade (ICB) shows limited efficacy in triple-negative breast cancer (TNBC).
  • Mechanisms underlying ICB resistance in TNBC are not fully understood.
  • Identifying novel regulators of antitumor immunity is crucial for improving TNBC treatment.

Purpose of the Study:

  • To identify regulators of antitumor immunity in TNBC.
  • To elucidate the role of FAM135B in T cell activation and ICB response.
  • To investigate the molecular mechanisms of FAM135B-mediated immune activation.

Main Methods:

  • Single-cell sequencing analysis of TNBC tumors.
  • Functional assays to assess T cell activity.
  • Co-immunoprecipitation and ubiquitination assays to study protein interactions.

Main Results:

  • FAM135B was identified as a key regulator of antitumor immunity in TNBC.
  • FAM135B activates cytotoxic T cells by stimulating the STING pathway.
  • FAM135B inhibits IFI16 ubiquitination and degradation, stabilizing IFI16 and initiating STING signaling.
  • Deubiquitination of IFI16 at specific lysine residues is essential for FAM135B's function.

Conclusions:

  • FAM135B enhances ICB efficacy in TNBC by promoting T cell activity through the IFI16-STING pathway.
  • FAM135B represents a potential biomarker for predicting ICB response in TNBC patients.
  • Targeting FAM135B or its downstream pathway could offer new therapeutic strategies for TNBC.

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