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SWI/SNF缺陷型恶性肿瘤:免疫肿瘤治疗的最佳候选对象?

SWI/SNF-deficient Malignancies: Optimal Candidates for Immune-oncological Therapy?

作者信息

Agaimy Abbas

机构信息

Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

出版信息

Adv Anat Pathol. 2023 May 1;30(3):211-217. doi: 10.1097/PAP.0000000000000366. Epub 2022 Sep 5.

DOI:10.1097/PAP.0000000000000366
PMID:36069856
Abstract

Inactivation of different subunits of the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex has emerged as one of the most frequent genetic pathways driving a variety of neoplasms of diverse histogenesis, originating in different organs. With few exceptions, most SWI/SNF-deficient malignancies pursue a highly aggressive clinical course resulting in widespread disease dissemination either at or soon after diagnosis, ultimately causing patients' death soon after diagnosis, despite the apparently curative treatment intention. To date, no satisfactorily effective systemic chemotherapy has been established for treating these diseases. This disappointing finding underlines the urgent need for an effective systemic therapy that would enable sufficient intermediate to long-term disease control. Recently, SWI/SNF-deficiency has increasingly emerged as pivotal in cancer immunogenicity and hence a promising biomarker predicting response to immune-checkpoint inhibition therapy utilizing several recently established drugs. This review summarizes the most recent literature on this topic with emphasis on the entities that most likely represent suitable candidates for immune therapy.

摘要

开关/蔗糖非发酵(SWI/SNF)染色质重塑复合物不同亚基的失活已成为驱动多种不同组织发生、起源于不同器官的肿瘤的最常见遗传途径之一。除少数例外,大多数SWI/SNF缺陷型恶性肿瘤的临床病程高度侵袭性,导致在诊断时或诊断后不久疾病广泛播散,尽管有明显的治愈性治疗意图,但最终仍导致患者在诊断后不久死亡。迄今为止,尚未建立令人满意的有效全身化疗方案来治疗这些疾病。这一令人失望的发现凸显了迫切需要一种有效的全身治疗方法,以实现足够的中长期疾病控制。最近,SWI/SNF缺陷在癌症免疫原性中越来越重要,因此成为一种有前景的生物标志物,可预测使用几种最近获批药物的免疫检查点抑制疗法的反应。本综述总结了关于该主题的最新文献,重点关注最有可能成为免疫治疗合适候选者的实体。

相似文献

1
SWI/SNF-deficient Malignancies: Optimal Candidates for Immune-oncological Therapy?SWI/SNF缺陷型恶性肿瘤:免疫肿瘤治疗的最佳候选对象?
Adv Anat Pathol. 2023 May 1;30(3):211-217. doi: 10.1097/PAP.0000000000000366. Epub 2022 Sep 5.
2
Hereditary SWI/SNF complex deficiency syndromes.遗传性SWI/SNF复合物缺陷综合征
Semin Diagn Pathol. 2018 May;35(3):193-198. doi: 10.1053/j.semdp.2018.01.002. Epub 2018 Feb 1.
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SWI/SNF Complex-Deficient Soft Tissue Neoplasms: A Pattern-Based Approach to Diagnosis and Differential Diagnosis.SWI/SNF复合物缺陷型软组织肿瘤:基于模式的诊断与鉴别诊断方法
Surg Pathol Clin. 2019 Mar;12(1):149-163. doi: 10.1016/j.path.2018.10.006.
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The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-NonFermentable (SWI/SNF) complex mutated ovarian cancer.新型可逆 LSD1 抑制剂 SP-2577 促进 SWI/SNF 复合物突变型卵巢癌中的抗肿瘤免疫。
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SWI/SNF chromatin remodeling and human malignancies.SWI/SNF 染色质重塑与人类恶性肿瘤。
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SWI/SNF Complex-deficient Undifferentiated/Rhabdoid Carcinomas of the Gastrointestinal Tract: A Series of 13 Cases Highlighting Mutually Exclusive Loss of SMARCA4 and SMARCA2 and Frequent Co-inactivation of SMARCB1 and SMARCA2.SWI/SNF复合物缺陷型胃肠道未分化/横纹肌样癌:13例病例系列研究,突出显示SMARCA4和SMARCA2的相互排斥性缺失以及SMARCB1和SMARCA2的频繁共同失活
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SWI/SNF deficient central nervous system neoplasms.SWI/SNF 缺陷型中枢神经系统肿瘤。
Semin Diagn Pathol. 2021 May;38(3):167-174. doi: 10.1053/j.semdp.2021.03.003. Epub 2021 Mar 15.
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SWI/SNF protein expression status in fumarate hydratase-deficient renal cell carcinoma: immunohistochemical analysis of 32 tumors from 28 patients.琥珀酸脱氢酶缺陷型肾细胞癌中 SWI/SNF 蛋白的表达状态:28 例患者 32 个肿瘤的免疫组化分析。
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Recent insights into the SWI/SNF complex and the molecular mechanism of hSNF5 deficiency in rhabdoid tumors.近期对 SWI/SNF 复合物的深入了解,以及横纹肌肉瘤中 hSNF5 缺失的分子机制。
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Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer.汇聚的结构改变将 SWItch/Sucrose NonFermentable(SWI/SNF)染色质重塑因子定义为胰腺癌中一个核心的肿瘤抑制复合物。
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):E252-9. doi: 10.1073/pnas.1114817109. Epub 2012 Jan 10.

引用本文的文献

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Small bowel metastatic SWI/SNF-deficient undifferentiated carcinoma may be predictive of lung primary-a rare presentation with novel SMARCA2 mutation findings in a study of three cases.小肠转移性SWI/SNF缺陷未分化癌可能提示原发性肺癌——在一项三例病例研究中的罕见表现及新型SMARCA2突变发现
Virchows Arch. 2025 Aug 7. doi: 10.1007/s00428-025-04208-0.
2
Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.调控细胞死亡及其在肿瘤进展中的表观遗传修饰的机制和串扰。
Mol Cancer. 2024 Nov 29;23(1):267. doi: 10.1186/s12943-024-02172-y.
3
Medullary carcinomas of the nonampullary small intestine: association with coeliac disease, mismatch repair deficiency, PD-L1 expression, and favourable prognosis.
非壶腹性小肠髓样癌:与乳糜泻、错配修复缺陷、PD-L1表达及良好预后的关联
Histopathology. 2025 Jan;86(2):236-246. doi: 10.1111/his.15307. Epub 2024 Aug 28.
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SMARCB1-deficient sinonasal adenocarcinoma: a rare variant of SWI/SNF-deficient malignancy often misclassified as high-grade non-intestinal-type sinonasal adenocarcinoma or myoepithelial carcinoma.SMARCB1 缺陷型鼻腔鼻窦腺癌:一种罕见的 SWI/SNF 缺陷型恶性肿瘤,常被误诊为高级别非肠型鼻腔鼻窦腺癌或肌上皮癌。
Virchows Arch. 2024 Aug;485(2):245-256. doi: 10.1007/s00428-023-03650-2. Epub 2023 Dec 12.
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Dysregulation of SWI/SNF Chromatin Remodelers in NSCLC: Its Influence on Cancer Therapies including Immunotherapy.非小细胞肺癌中 SWI/SNF 染色质重塑因子的失调:对包括免疫疗法在内的癌症疗法的影响。
Biomolecules. 2023 Jun 13;13(6):984. doi: 10.3390/biom13060984.
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The roles of the SWI/SNF complex in cancer.SWI/SNF复合物在癌症中的作用。
Cancer Cytopathol. 2023 Jul;131(7):410-414. doi: 10.1002/cncy.22691. Epub 2023 Apr 4.