CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Breast Cancer Immunotherapy: A Team Science Approach.
Breast Cancer Immunotherapy: A Team Science Approach.
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免疫治疗已重塑多种恶性肿瘤(包括乳腺癌)的治疗格局。乳腺癌过去被认为免疫原性较低,但特别是三阴性亚型(TNBC)已显示对免疫检查点抑制剂(ICI)有应答。TNBC 的特点是肿瘤突变负荷较高、PD-L1 表达升高及 TIL 增多,使其成为免疫治疗开发的重点。在 PD-L1 表达的转移性 TNBC 中,KEYNOTE-355 等试验显示,在化疗基础上加入 pembrolizumab 可改善 PFS 和 OS,因此该方案获监管批准。在早期 TNBC 中,KEYNOTE-522 证实新辅助化疗联合 ICI 已成为 II、III 期肿瘤标准治疗;关键临床试验显示,无论 PD-L1 表达状态如何,病理完全缓解和无事件生存期均获改善。ICI 用于 HER2 阳性及激素受体阳性/HER2 阴性等其他亚型仍在积极研究。持续开展的研究还探索新策略,包括双免疫检查点阻断、细胞疗法(如 CAR-T、TIL)、癌症疫苗,以及与靶向药物和抗体药物偶联物(ADC)的合理联合。PD-L1、肿瘤突变负荷、免疫基因特征和肠道微生物组等生物标志物正用于优化患者筛选并预测应答。
此外,有效管理免疫相关毒性至关重要,尤其是在以治愈为目标的治疗场景。随着免疫治疗作用扩大,多学科、生物标志物驱动的方法对于优化结局并拓宽其在不同乳腺癌亚型中的应用至关重要。
Immunotherapy has reshaped the treatment landscape of several malignancies, including breast cancer. While historically considered less immunogenic, breast cancer-particularly the triple-negative subtype (TNBC)-has demonstrated responsiveness to immune checkpoint inhibitors (ICIs). TNBC is characterized by higher tumor mutational burden, elevated PD-L1 expression, and increased tumor-infiltrating lymphocytes, making it a leading focus of immunotherapy development. In metastatic TNBC with PD-L1 expression, trials such as KEYNOTE-355 have shown improvements in progression-free and overall survival with the addition of the ICI, pembrolizumab to chemotherapy, leading to regulatory approval.
In early-stage TNBC, KEYNOTE-522 established a neoadjuvant chemotherapy plus ICI as the standard of care for stage II and III tumors. This was based on improved pathologic complete response and event-free survival in this pivotal clinical trial regardless of PD-L1 expression. ICIs in other subtypes, such as HER2-positive and hormone receptor-positive/HER2-negative disease, remain under active investigation.
Ongoing studies are also exploring novel strategies including dual immune checkpoint blockade, cellular therapies (e. g. , CAR-T, TILs), cancer vaccines, and rational combinations with targeted agents and antibody-drug conjugates (ADCs). Biomarkers such as PD-L1, tumor mutational burden, immune gene signatures, and the gut microbiome are being evaluated to refine patient selection and predict response.
Additionally, effective management of immune-related toxicities is critical, particularly in curative-intent settings. As the role of immunotherapy expands, a multidisciplinary, biomarker-driven approach will be essential to optimize outcomes and broaden its applicability across breast cancer subtypes.
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