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冷肿瘤和热肿瘤:从分子机制到靶向治疗。

Cold and hot tumors: from molecular mechanisms to targeted therapy.

机构信息

Department of Neurology, The Fourth Affiliated Hospital, China Medical University, Shenyang, China.

Department of Youth League Committee, The Fourth Affiliated Hospital, China Medical University, Shenyang, China.

出版信息

Signal Transduct Target Ther. 2024 Oct 18;9(1):274. doi: 10.1038/s41392-024-01979-x.


DOI:10.1038/s41392-024-01979-x
PMID:39420203
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11491057/
Abstract

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which has shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment in cancer therapy, only a minority of patients exhibit a positive response to it. In patients with solid tumors, those who respond well to ICB treatment typically demonstrate an active immune profile referred to as the "hot" (immune-inflamed) phenotype. On the other hand, non-responsive patients may exhibit a distinct "cold" (immune-desert) phenotype, differing from the features of "hot" tumors. Additionally, there is a more nuanced "excluded" immune phenotype, positioned between the "cold" and "hot" categories, known as the immune "excluded" type. Effective differentiation between "cold" and "hot" tumors, and understanding tumor intrinsic factors, immune characteristics, TME, and external factors are critical for predicting tumor response and treatment results. It is widely accepted that ICB therapy exerts a more profound effect on "hot" tumors, with limited efficacy against "cold" or "altered" tumors, necessitating combinations with other therapeutic modalities to enhance immune cell infiltration into tumor tissue and convert "cold" or "altered" tumors into "hot" ones. Therefore, aligning with the traits of "cold" and "hot" tumors, this review systematically delineates the respective immune characteristics, influencing factors, and extensively discusses varied treatment approaches and drug targets based on "cold" and "hot" tumors to assess clinical efficacy.

摘要

免疫疗法在癌症治疗方面取得了重大进展,特别是通过免疫检查点阻断(ICB),在各种肿瘤类型中都显示出显著的临床益处。尽管 ICB 治疗在癌症治疗中具有变革性的影响,但只有少数患者对此有积极的反应。在实体瘤患者中,对 ICB 治疗反应良好的患者通常表现出一种活跃的免疫特征,称为“热”(免疫激活)表型。另一方面,无反应的患者可能表现出明显的“冷”(免疫荒漠)表型,与“热”肿瘤的特征不同。此外,还有一种更为微妙的“排除”免疫表型,位于“冷”和“热”之间,称为免疫“排除”型。有效地区分“冷”和“热”肿瘤,了解肿瘤内在因素、免疫特征、TME 和外部因素,对于预测肿瘤反应和治疗结果至关重要。人们普遍认为,ICB 治疗对“热”肿瘤的作用更为显著,对“冷”或“改变”肿瘤的疗效有限,因此需要与其他治疗方式联合使用,以增强免疫细胞浸润肿瘤组织,并将“冷”或“改变”肿瘤转化为“热”肿瘤。因此,本综述根据“冷”和“热”肿瘤的特点,系统地描述了各自的免疫特征、影响因素,并广泛讨论了基于“冷”和“热”肿瘤的不同治疗方法和药物靶点,以评估临床疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/44592675c7bc/41392_2024_1979_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/59da1459f501/41392_2024_1979_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/25ba9826e95b/41392_2024_1979_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/28a1b0eb47ae/41392_2024_1979_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/f9619ab8e3bd/41392_2024_1979_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/4bb5122c73ff/41392_2024_1979_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/6d9ffa6c5eab/41392_2024_1979_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/2313ee4b2a93/41392_2024_1979_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/44592675c7bc/41392_2024_1979_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/59da1459f501/41392_2024_1979_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/25ba9826e95b/41392_2024_1979_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/28a1b0eb47ae/41392_2024_1979_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/f9619ab8e3bd/41392_2024_1979_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/4bb5122c73ff/41392_2024_1979_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/6d9ffa6c5eab/41392_2024_1979_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/2313ee4b2a93/41392_2024_1979_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80b/11491057/44592675c7bc/41392_2024_1979_Fig8_HTML.jpg

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本文引用的文献

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J Immunother Cancer. 2024-5-31

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