Surgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA.
Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.
Limited evidence exists that humans mount a mutation-specific T cell response to epithelial cancers. We used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (T(H)1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional T(H)1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease. Upon disease progression, the patient was retreated with a >95% pure population of mutation-reactive T(H)1 cells and again experienced tumor regression. These results provide evidence that a CD4+ T cell response against a mutated antigen can be harnessed to mediate regression of a metastatic epithelial cancer.
目前有限的证据表明人类对上皮性癌症会产生突变特异性 T 细胞反应。我们采用基于全外显子组测序的方法证明，一名转移性胆管癌患者的肿瘤浸润淋巴细胞（TIL）中含有识别癌症中表达的表皮生长因子受体 2 相互作用蛋白（ERBB2IP）突变的 CD4+辅助性 T 细胞 1（T(H)1）。在输注约 25%的突变特异性多功能 T(H)1 细胞的 TIL 后，患者的靶病变减少，疾病稳定时间延长。疾病进展时，患者用>95%的纯突变反应性 T(H)1 细胞进行再治疗，再次经历肿瘤消退。这些结果提供了证据，表明针对突变抗原的 CD4+T 细胞反应可用于介导转移性上皮性癌症的消退。
