Male-biased Yap1-Cd276/B7-H3 axis for immune evasion in medulloblastoma.
Document Type
Article
Publication Date
4-13-2026
Original Citation
Abdelfattah N,
Natarajan S,
Tran H,
Wong T,
Faisal M,
Maldonado J,
McMinimy R,
Borland H,
Chen S,
Zhao H,
Vasquez M,
Rodriguez F,
Wagner C,
Camargo F,
Olson J,
George J,
Yun K.
Male-biased Yap1-Cd276/B7-H3 axis for immune evasion in medulloblastoma. Cancer cell. 2026; 44(4):760
Keywords
JGM, JMG, Medulloblastoma, Animals, Humans, YAP-Signaling Proteins, Male, Female, B7 Antigens, Mice, Adaptor Proteins, Signal Transducing, Transcription Factors, Cerebellar Neoplasms, Cell Line, Tumor, CD8-Positive T-Lymphocytes, Sex Factors, Tumor Escape
ISSN
1878-3686
PMID
41650973
DOI
https://doi.org/10.1016/j.ccell.2026.01.005
Abstract
Molecular mechanisms underlying sex-specific differences in cancer incidence and therapy responses are under intense investigation. Here, we report sex-biased functions of Yap1 in multiple cancer types in human and mouse. Through integrated multi-omics analyses, we demonstrate that Yap1 deletion significantly extends survival in male but not female Sonic Hedgehog (SHH) medulloblastomas (MB) models. While Yap1 is required to maintain stem-like cells in both sexes, Yap1 plays a more critical role in immune evasion in males. Mechanistically, YAP1 is essential for activating Cd276/B7-H3 expression to mediate CD8+ T cell suppression in males. Consistently, CD276 inhibition extends survival in male but not female SHH MB. Moreover, in vivo targets of YAP1 stratify survival in male but not female patients with medulloblastoma, glioblastoma, mesothelioma, and lung cancer. This study provides evidence for sex-biased functions of Yap1 and CD276 in MB immune suppression and highlights the importance of biological sex in cancer:immune interactions.