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T细胞在头颈部鳞状细胞癌中的作用:从免疫到免疫治疗。

The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy.

作者信息

Damasio Marcos Paulo S, Nascimento Camila Sales, Andrade Lidia M, de Oliveira Vivian L, Calzavara-Silva Carlos Eduardo

机构信息

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Grupo de pesquisa em Imunologia Celular e Molecular, Fundação Oswaldo Cruz, Instituto Rene Rachou, Belo Horizonte, MG, Brazil.

出版信息

Front Oncol. 2022 Oct 20;12:1021609. doi: 10.3389/fonc.2022.1021609. eCollection 2022.

Abstract

Head and neck squamous cell carcinoma (HNSCC) encompass a group of complex entities of tumours affecting the aerodigestive upper tract. The main risk factors are strongly related to tobacco and alcohol consumption, but also HPV infection is often associated. Surgery, radiotherapy and/or chemotherapy are the standard treatments, though the 5-year overall survival is less than 50%. The advances in genomics, molecular medicine, immunology, and nanotechnology have shed a light on tumour biology which helps clinical researchers to obtain more efficacious and less toxic therapies. Head and neck tumours possess different immune escape mechanisms including diminishing the immune response through modulating immune checkpoints, in addition to the recruitment and differentiation of suppressive immune cells. The insights into the HNSCC biology and its strong interaction with the tumour microenvironment highlights the role of immunomodulating agents. Recently, the knowledge of the immunological features of these tumours has paved the way for the discovery of effective biomarkers that allow a better selection of patients with odds of improving overall survival through immunotherapy. Specially biomarkers regarding immune checkpoint inhibitors antibodies, such as anti-PD-1/PD-L1 and anti-CTLA-4 in combination with standard therapy or as monotherapy. New immunotherapies to treat head and neck cancer carcinomas, such as CAR T cells and nanoparticles have been the center of attention and in this review, we discuss the necessity of finding targets for the T cell in the cancer cells to generate CAR T cells, but also the relevance of evaluating specificity and safety of those therapies.

摘要

头颈部鳞状细胞癌(HNSCC)包括一组影响上呼吸道消化道的复杂肿瘤实体。主要危险因素与烟草和酒精消费密切相关,但人乳头瘤病毒(HPV)感染也常常与之相关。手术、放疗和/或化疗是标准治疗方法,不过5年总生存率低于50%。基因组学、分子医学、免疫学和纳米技术的进展揭示了肿瘤生物学,这有助于临床研究人员获得更有效且毒性更小的治疗方法。头颈部肿瘤具有不同的免疫逃逸机制,包括通过调节免疫检查点来减弱免疫反应,以及招募和分化抑制性免疫细胞。对头颈部鳞状细胞癌生物学及其与肿瘤微环境的强烈相互作用的深入了解突出了免疫调节药物的作用。最近,对这些肿瘤免疫特征的认识为发现有效的生物标志物铺平了道路,这些生物标志物能够更好地选择有可能通过免疫疗法提高总生存率的患者。特别是关于免疫检查点抑制剂抗体的生物标志物,如抗PD-1/PD-L1和抗CTLA-4,可与标准疗法联合使用或作为单一疗法。治疗头颈部癌的新免疫疗法,如嵌合抗原受体(CAR)T细胞和纳米颗粒,一直是人们关注的焦点,在本综述中,我们讨论了在癌细胞中寻找CAR T细胞的T细胞靶点的必要性,以及评估这些疗法的特异性和安全性的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce34/9632296/87f105437913/fonc-12-1021609-g001.jpg

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