2018年6月22日，全球自然科学三大旗舰期刊之一、美国科学促进会《科学》正刊发表资深编辑葆拉·基伯斯蒂斯的研究报道：晚期乳腺癌一线希望。
免疫疗法正在彻底改变癌症治疗。通过细胞分裂周期检查点阻断剂或者抗肿瘤淋巴细胞等免疫疗法，可以有效治疗体细胞突变水平高的癌症（例如黑素瘤、吸烟诱发肺癌、膀胱癌）。不过，免疫疗法对于其他突变水平较低的常见上皮癌（例如胃肠癌、乳腺癌、卵巢癌）往往无效。其中原因之一为乳腺癌等上皮癌表达的新生抗原或肿瘤相关基因突变蛋白质相对较少，无法被免疫系统精准攻击。通过一种被称为过继免疫或过继转移的被动免疫策略，采集已被免疫个体的免疫细胞、免疫分子或抗体，将其输入另一个体而使之被动获得相应的特异性细胞免疫功能，即将接触过抗原的个体（供体）所具有的免疫反应性被动地转移给未被免疫的个体（受体），能够解决上述问题。既往研究已经发现，将专门针对体细胞突变基因编码蛋白质的自体肿瘤浸润淋巴细胞注射给患者自己，对于转移性胆管癌、结肠癌、宫颈癌，可使肿瘤消散。
英国《自然》旗下《自然医学》2018年第6期正式发表美国国家卫生研究院国家癌症研究所、弗吉尼亚联邦大学医学院的病例研究，报告了一例转移性乳腺癌患者接受体外培养后仅对4种新生抗原有反应的自体肿瘤浸润淋巴细胞治疗，产生了激动人心的临床疗效。
该患者为一例对多种化疗方案无效的激素受体阳性HER2阴性转移性乳腺癌女性。首先，将其乳腺癌细胞进行基因测序，发现4种体细胞突变基因编码蛋白质（SLC3A2、KIAA0368、CADPS2、CTSB）。随后，将其肿瘤浸润淋巴细胞进行体外培养繁殖至数十亿，从中筛选能够精准攻击患者乳腺癌细胞4种蛋白质突变型并进一步培养繁殖。最后，将大约820亿专门针对体细胞突变蛋白的致敏胸腺依赖型肿瘤浸润淋巴细胞（T细胞）注射给患者自己，并且联合白细胞介素2和检查点阻断剂，转移性乳腺癌已经完全持久消散超过22个月。
因此，这是一种治疗此类患者的新型免疫疗法，该研究结果也为其他免疫疗法难治型癌症的研究奠定了基础。
对此，加拿大多伦多的安大略癌症研究所发表同期述评：精准攻击乳腺癌的肿瘤体细胞突变蛋白质。
Nat Med. 2018 Jun 4;24(6):724-730.
Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer.
Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, Gartner J, Jia L, Trebska-McGowan K, Somerville RP, Robbins PF, Rosenberg SA, Goff SL, Feldman SA.
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins - SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.
PMID: 29867227
DOI: 10.1038/s41591-018-0040-8
Nat Med. 2018 Jun 4;24(6):703-704.
Targeting the cancer mutanome of breast cancer.
Radvanyi LG.
Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
A metastatic hormone receptor-positive breast cancer, usually resistant to immunotherapy, is successfully treated with tumor-infiltrating lymphocytes enriched for neoantigen reactivity, underscoring the broad potential of this immunotherapeutic approach.
PMID: 29867234
DOI: 10.1038/s41591-018-0065-z
Science. 2018 Jun 22;360(6395):1311-1312.
A ray of hope for advanced breast cancer.
Paula A. Kiberstis.
Immunotherapies are revolutionizing cancer treatment. Yet certain common cancer types, such as breast cancer, are often missing from the immunotherapy conversation. One reason is that breast cancers express relatively few neoantigens, or mutant tumor-associated proteins that are targeted by the immune system. A case study now shows that in the setting of adoptive T cell therapy, this problem can be circumvented, resulting in a dramatic clinical response. Zacharakis et al. report that a patient with metastatic breast cancer showed complete durable remission of her disease after being treated with autologous tumor-infiltrating lymphocytes that had been enriched ex vivo for reactivity to just four neoantigens. This study lays the groundwork for studies of other cancers assumed to be refractory to immunotherapy.
DOI: 10.1126/science.360.6395.1311-d
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