美国休斯顿卫理公会研究所Kyuson Yun小组取得一项新突破。他们研制了男性偏倚的Yap1-Cd276/B7-H3轴在成神经管细胞瘤中的免疫逃避。相关论文于2026年2月5日发表在《癌细胞》杂志上。

该课题组研究人员报道了Yap1在人类和小鼠的多种癌症类型中的性别偏倚功能。通过综合多组学分析，该课题组研究人员证明Yap1缺失显著延长了男性而非女性Sonic Hedgehog （SHH）髓母细胞瘤（MB）模型的生存期。虽然Yap1在两性中都需要维持干细胞样细胞，但在男性的免疫逃避中，Yap1起着更关键的作用。在机制上，YAP1是激活Cd276/B7-H3表达介导CD8⁺ T细胞抑制的必要条件。一致地，CD276抑制延长了男性SHH MB的存活，而不是女性SHH MB。

此外，YAP1的体内靶点在男性髓母细胞瘤、胶质母细胞瘤、间皮瘤和肺癌患者中分层生存，而不是女性患者。这项研究为Yap1和CD276在MB免疫抑制中的性别偏向功能提供了证据，并强调了生物学性别在癌症免疫相互作用中的重要性。

据了解，癌症发病率和治疗反应的性别差异背后的分子机制正在深入研究中。

附：英文原文

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

Author: Nourhan Abdelfattah, Sivaraman Natarajan, Han Nhat Tran, Thomas Wong, Maryam Faisal, Jose Maldonado, Rachael McMinimy, Hannah Borland, Shu-hsia Chen, Hong Zhao, Matthew Vasquez, Freddys F. Rodriguez, Carston R. Wagner, Fernando Camargo, James Olson, Joshy George, Kyuson Yun

Issue&Volume: 2026-02-05

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.

DOI: 10.1016/j.ccell.2026.01.005

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(26)00044-9