研究概要
乳腺癌仍是全球癌症相关发病率和死亡率的主要原因,其治疗反应受每种乳腺癌亚型独特生物学特征的影响。
中文摘要
乳腺癌仍然是全球癌症相关发病率和死亡率的主要原因之一,其治疗反应受到每种乳腺癌亚型独特生物学特征的塑造。免疫治疗已成为特定疾病亚型中的一种变革性方法,其中最成功的结果见于三阴性乳腺癌(TNBC)。免疫检查点抑制剂(ICIs)已改变了许多实体瘤的治疗格局。在乳腺癌中,它们与化疗联合时已在TNBC中显示出临床获益,确立了早期和转移性阶段的新标准治疗。然而,大多数乳腺癌对检查点阻断表现出内在或获得性耐药,这是由低肿瘤免疫原性和免疫抑制性肿瘤微环境驱动的。细胞免疫治疗的最新进展可能代表乳腺癌治疗领域的下一个前沿。靶向HER2、ROR1、MUC1、间皮素和B7-H3等抗原的嵌合抗原受体(CAR)T细胞正在进入早期临床评估,其结果备受期待。平行方法,包括TIL(肿瘤浸润淋巴细胞)治疗、T细胞受体(TCR)工程化T细胞和CAR-自然杀伤(CAR-NK)平台,提供了克服抗原呈递障碍和免疫逃逸的替代机制。本综述总结了乳腺癌免疫治疗的当前临床证据,重点介绍了新兴的细胞策略,并讨论了关键挑战,包括抗原特异性、脱靶毒性和肿瘤微环境介导的耐药。未来的进展可能取决于合理的联合方案和下一代工程化免疫细胞平台,以实现持久且个性化的临床获益。
展开英文摘要原文
Breast cancer remains a leading cause of cancer-related morbidity and mortality worldwide, with therapeutic response being shaped by the unique biology of each breast cancer subtype. Immunotherapy has emerged as a transformative approach in selected disease subtypes, with the most successful results being found in relation to triple negative breast cancer (TNBC). Immune checkpoint inhibitors (ICIs) have transformed the management of many solid tumours. In breast cancer, they have demonstrated clinical benefit in TNBC when combined with chemotherapy, establishing a new standard of care in both early-stage and metastatic settings. However, the majority of breast cancers exhibit intrinsic or acquired resistance to checkpoint blockade, driven by low tumour immunogenicity and an immunosuppressive tumour microenvironment. Recent advances in cellular immunotherapy could represent the next frontier in the therapeutic landscape of breast cancer. Chimeric antigen receptor (CAR) T cell targeting antigens such as HER2, ROR1, MUC1, mesothelin, and B7-H3 are entering early-phase clinical evaluation with results eagerly awaited. Parallel approaches, including tumour-infiltrating lymphocyte (TIL) therapy, T cell receptor (TCR)-engineered T cells, and CAR-natural killer (CAR-NK) platforms, offer alternative mechanisms to overcome antigen presentation barriers and immune evasion. This review summarises current clinical evidence for immunotherapies in breast cancer, highlights emerging cellular strategies, and discusses key challenges including antigen specificity, off-tumour toxicity, and tumour microenvironment-mediated resistance. Future progress will likely depend on rational combination approaches and next-generation engineered immune cell platforms to achieve durable and personalised clinical benefit.
论文信息
- 作者
- Tsagkaraki I、Gannon I、Rampotas A、Singh D、Roddy H、Ottaviani D、Roddie C
- 第一作者单位
- Oncology Department, Royal Berkshire NHS Foundation Trust, Reading RG1 5AN, UK.United Kingdom
- 通讯作者单位
- Haematology Department, Cancer Institute, University College, London WC1E 6DD, UK.United Kingdom
- 文献类型
- 综述
- 期刊
- Cancers2026 Mar 11