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Male-biased Yap1-Cd276/B7-H3 axis for immune evasion in medulloblastoma

Nourhan Abdelfattah1, Sivaraman Natarajan2, Han Nhat Tran1

  • 1Department of Neurology, Houston Methodist Research Institute, Houston, TX 77030, USA.

Cancer Cell
|February 6, 2026
PubMed

Insights

Sex-biased Yap1 functions impact cancer immunity. Yap1 deletion improves male survival in Sonic Hedgehog medulloblastoma by enhancing immune response, unlike in females.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Sex-specific differences in cancer incidence and treatment outcomes are significant.
  • The molecular underpinnings of these sex biases are not fully understood.

Purpose of the Study:

  • To investigate the sex-biased roles of Yap1 in cancer, particularly in Sonic Hedgehog medulloblastoma (SHH MB).
  • To elucidate the mechanisms by which Yap1 influences cancer immunity in a sex-specific manner.

Main Methods:

  • Integrated multi-omics analyses in human and mouse cancer models.
  • Yap1 deletion and CD276 inhibition experiments in vivo.
  • Analysis of Yap1 targets in patient data for medulloblastoma, glioblastoma, mesothelioma, and lung cancer.

Main Results:

  • Yap1 deletion extended survival in male but not female SHH MB models.
  • Yap1 is crucial for immune evasion in males by upregulating CD276/B7-H3, which suppresses CD8+ T cells.
  • CD276 inhibition improved survival in male but not female SHH MB.
  • Yap1 targets predict survival differently in males versus females across multiple cancer types.

Conclusions:

  • Yap1 exhibits sex-biased functions in cancer, particularly in regulating immune responses.
  • CD276 is a key mediator of Yap1's sex-specific immune suppressive role in SHH MB.
  • Biological sex is a critical factor in cancer-immune interactions and therapeutic strategies.
Keywords:
CD276/ B7-H3YAP1brain tumorcancer stem cellsimmune evasionimmunotherapymedulloblastomasex biastumor microenvironment

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