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乳腺癌的免疫格局:克服免疫治疗耐药的策略

英文原题:The Immune Landscape of Breast Cancer: Strategies for Overcoming Immunotherapy Resistance.

查看英文原题

The Immune Landscape of Breast Cancer: Strategies for Overcoming Immunotherapy Resistance.

PubMed 2021/11/29(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

传统上,乳腺癌(BC)被认为本身免疫原性不足,肿瘤内免疫细胞浸润也不充分。因此长期以来,人们认为靶向乳腺癌及其微环境的免疫疗法缺乏依据,不会使乳腺癌患者获益。然而,迄今已有大量报告指出,TIL(肿瘤浸润淋巴细胞)是乳腺癌具有预后和临床意义的生物标志物。在HER2阳性乳腺癌和三阴性乳腺癌(TNBC)患者中,无论治疗前还是接受辅助或新辅助化疗后,原发肿瘤均可见较高TIL表达。晚期TNBC免疫治疗的另一重要进展是应用靶向PD-L1的免疫检查点抑制剂。尽管这些发现以及近期CAR-T 细胞疗法的发展,为显著推进乳腺癌治疗带来巨大希望,免疫治疗药物要在乳腺癌治疗中达到最佳效果仍面临多种障碍。其中关键障碍是免疫抑制性肿瘤微环境,它严重阻碍免疫疗法治疗侵袭性最强的乳腺癌类型——HER2阳性和TNBC。因此,亟需改进现有免疫疗法并开发新的免疫治疗策略。

展开英文摘要原文

Breast cancer (BC) has traditionally been considered to be not inherently immunogenic and insufficiently represented by immune cell infiltrates.

Therefore, for a long time, it was thought that the immunotherapies targeting this type of cancer and its microenvironment were not justified and would not bring benefits for breast cancer patients. Nevertheless, to date, a considerable number of reports have indicated tumor-infiltrating lymphocytes (TILs) as a prognostic and clinically relevant biomarker in breast cancer. A high TILs expression has been demonstrated in primary tumors, of both, HER2-positive BC and triple-negative (TNBC), of patients before treatment, as well as after treatment with adjuvant and neoadjuvant chemotherapy.

Another milestone was reached in advanced TNBC immunotherapy with the help of the immune checkpoint inhibitors directed against the PD-L1 molecule. Although those findings, together with the recent developments in chimeric antigen receptor T cell therapies, show immense promise for significant advancements in breast cancer treatments, there are still various obstacles to the optimal activity of immunotherapeutics in BC treatment.

Of these, the immunosuppressive tumor microenvironment constitutes a key barrier that greatly hinders the success of immunotherapies in the most aggressive types of breast cancer, HER2-positive and TNBC.

Therefore, the improvement of the current and the demand for the development of new immunotherapeutic strategies is strongly warranted.

论文信息

作者
Retecki K、Seweryn M、Graczyk-Jarzynka A、Bajor M
第一作者单位
Department of Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland.Poland
通讯作者单位
Laboratory of Immunology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland.Poland
文献类型
综述
期刊
Cancers2021 Nov 29
原文标识
PubMed 34885122 · DOI 10.3390/cancers13236012