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GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery
Cell Reports Medicine ( IF 11.7 ) Pub Date : 2024-05-10 , DOI: 10.1016/j.xcrm.2024.101557
Casper W F van Eijck 1 , Francisco X Real 2 , Núria Malats 3 , Disha Vadgama 4 , Thierry P P van den Bosch 4 , Michail Doukas 4 , Casper H J van Eijck 1 , Dana A M Mustafa 5 ,
Cell Reports Medicine ( IF 11.7 ) Pub Date : 2024-05-10 , DOI: 10.1016/j.xcrm.2024.101557
Casper W F van Eijck 1 , Francisco X Real 2 , Núria Malats 3 , Disha Vadgama 4 , Thierry P P van den Bosch 4 , Michail Doukas 4 , Casper H J van Eijck 1 , Dana A M Mustafa 5 ,
Affiliation
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This study underscores GATA6’s role in distinguishing classical and basal-like pancreatic ductal adenocarcinoma (PDAC) phenotypes. Retrospective studies associate GATA6 immunohistochemistry (IHC) expression with survival outcomes, warranting prospective validation. In a prospective treatment-naive cohort of patients with resected PDAC, GATA6 IHC proves a prognostic discriminator, associating high GATA6 expression with extended survival and the classical PDAC phenotype. However, GATA6’s prognostic significance is numerically lower after gemcitabine-based neoadjuvant chemoradiotherapy compared to its significance in patients treated with upfront surgery. Furthermore, GATA6 is implicated in immunomodulation, although a comprehensive investigation of its immunological role is lacking. Treatment-naive PDAC tumors with varying GATA6 expression yield distinct immunological landscapes. Tumors highly expressing GATA6 show reduced infiltration of immunosuppressive regulatory T cells and M2 macrophages but increased infiltration of immune-stimulating, antigen-presenting, and activated T cells. Our findings caution against solely relying on GATA6 for molecular subtyping in clinical trials and open avenues for exploring immune-based combination therapies.
中文翻译：
GATA6 确定了一种免疫富集表型，该表型与接受前期手术的胰腺癌患者的良好预后相关
本研究强调了 GATA6 在区分经典和基底样胰腺导管腺癌 （PDAC） 表型中的作用。回顾性研究将 GATA6 免疫组化 （IHC） 表达与生存结果相关联，值得前瞻性验证。在已切除的 PDAC 患者的前瞻性初治队列中，GATA6 IHC 证明了预后鉴别因素，将 GATA6 高表达与延长生存期和经典 PDAC 表型相关联。然而，与接受前期手术治疗的患者相比，基于吉西他滨的新辅助放化疗后 GATA6 的预后意义在数值上较低。此外，GATA6 与免疫调节有关，尽管缺乏对其免疫作用的全面研究。具有不同 GATA6 表达的初治 PDAC 肿瘤产生不同的免疫学景观。高表达 GATA6 的肿瘤显示免疫抑制调节性 T 细胞和 M2 巨噬细胞的浸润减少，但免疫刺激、抗原呈递和活化 T 细胞的浸润增加。我们的研究结果告诫不要在临床试验中仅依赖 GATA6 进行分子亚型，并为探索基于免疫的联合疗法开辟了途径。
更新日期：2024-05-10
中文翻译：
GATA6 确定了一种免疫富集表型，该表型与接受前期手术的胰腺癌患者的良好预后相关
本研究强调了 GATA6 在区分经典和基底样胰腺导管腺癌 （PDAC） 表型中的作用。回顾性研究将 GATA6 免疫组化 （IHC） 表达与生存结果相关联，值得前瞻性验证。在已切除的 PDAC 患者的前瞻性初治队列中，GATA6 IHC 证明了预后鉴别因素，将 GATA6 高表达与延长生存期和经典 PDAC 表型相关联。然而，与接受前期手术治疗的患者相比，基于吉西他滨的新辅助放化疗后 GATA6 的预后意义在数值上较低。此外，GATA6 与免疫调节有关，尽管缺乏对其免疫作用的全面研究。具有不同 GATA6 表达的初治 PDAC 肿瘤产生不同的免疫学景观。高表达 GATA6 的肿瘤显示免疫抑制调节性 T 细胞和 M2 巨噬细胞的浸润减少，但免疫刺激、抗原呈递和活化 T 细胞的浸润增加。我们的研究结果告诫不要在临床试验中仅依赖 GATA6 进行分子亚型，并为探索基于免疫的联合疗法开辟了途径。
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