基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
过继性自然杀伤(NK)细胞疗法是治疗三阴性乳腺癌的一种有前景的策略,但其疗效往往受到瘤内持久性差以及在免疫抑制性肿瘤微环境中功能耗竭的限制。
英文原题:Immunomodulating Therapies in Breast Cancer-From Prognosis to Clinical Practice.
Immunomodulating Therapies in Breast Cancer-From Prognosis to Clinical Practice.
免疫系统在乳腺癌中的作用已经争论了几十年。
免疫系统在乳腺癌中的作用已经争论了几十年。下一代测序(NGS)等技术的出现,阐明了肿瘤体细胞突变导致新抗原与免疫反应之间的关键相互作用,从而增加TIL(肿瘤浸润淋巴细胞)并改善乳腺癌患者的预后。特别是,与其他乳腺癌亚型相比,三阴性乳腺癌(TNBC)具有更高的突变负荷。此外,更高水平的肿瘤相关抗原表明,免疫疗法是一种有前景的治疗选择,特别是对于TNBC。事实上,更高浓度的TIL(肿瘤浸润淋巴细胞)与TNBC更好的预后和化疗反应相关。癌症免疫细胞周期中的一个重要靶点是“免疫检查点”。免疫检查点抑制剂(ICPis)阻断某些作为免疫反应“刹车”的细胞表面蛋白的相互作用。近期研究表明,ICPis可改善早期和晚期TNBC的生存。然而,这是以增加毒性为代价的,尤其是免疫介导的毒性。作为一种替代方法,针对肿瘤相关新抗原的个体化mRNA疫苗接种策略代表了另一种有前景的方法,可诱导新抗原特异性免疫反应。这些新策略应有助于改善治疗结局,尤其是对于三阴性乳腺癌患者。
The role of the immune system in breast cancer has been debated for decades. The advent of technologies such as next generation sequencing (NGS) has elucidated the crucial interplay between somatic mutations in tumors leading to neoantigens and immune responses with increased tumor-infiltrating lymphocytes and improved prognosis of breast cancer patients. In particular, triple-negative breast cancer (TNBC) has a higher mutational burden compared to other breast cancer subtypes. In addition, higher levels of tumor-associated antigens suggest that immunotherapies are a promising treatment option, specifically for TNBC. Indeed, higher concentrations of tumor-infiltrating lymphocytes are associated with better prognosis and response to chemotherapy in TNBC. An important target within the cancer immune cell cycle is the "immune checkpoint". Immune checkpoint inhibitors (ICPis) block the interaction of certain cell surface proteins that act as "brakes" on immune responses. Recent studies have shown that ICPis improve survival in both early and advanced TNBC. However, this comes at the price of increased toxicity, particularly immune-mediated toxicity. As an alternative approach, individualized mRNA vaccination strategies against tumor-associated neoantigens represent another promising approach leading to neoantigen-specific immune responses. These novel strategies should help to improve treatment outcomes, especially for patients with triple negative breast cancer.
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