Department of Cancer Immunology, Oslo University Hospital Radiumhospitalet, Oslo, Norway. K. G. Jebsen Centers for Cancer Immunotherapy and for Inflammation Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
Science. 2016 Jun 10;352(6291):1337-41. doi: 10.1126/science.aaf2288. Epub 2016 May 19.
Accumulating evidence suggests that clinically efficacious cancer immunotherapies are driven by T cell reactivity against DNA mutation-derived neoantigens. However, among the large number of predicted neoantigens, only a minority is recognized by autologous patient T cells, and strategies to broaden neoantigen-specific T cell responses are therefore attractive. We found that naïve T cell repertoires of healthy blood donors provide a source of neoantigen-specific T cells, responding to 11 of 57 predicted human leukocyte antigen (HLA)-A*02:01-binding epitopes from three patients. Many of the T cell reactivities involved epitopes that in vivo were neglected by patient autologous tumor-infiltrating lymphocytes. Finally, T cells redirected with T cell receptors identified from donor-derived T cells efficiently recognized patient-derived melanoma cells harboring the relevant mutations, providing a rationale for the use of such "outsourced" immune responses in cancer immunotherapy.
越来越多的证据表明，临床上有效的癌症免疫疗法是由 T 细胞对 DNA 突变衍生的新抗原的反应驱动的。然而，在大量预测的新抗原中，只有少数被自体患者 T 细胞识别，因此拓宽新抗原特异性 T 细胞反应的策略具有吸引力。我们发现，健康献血者的幼稚 T 细胞库为新抗原特异性 T 细胞提供了来源，这些 T 细胞可识别来自 3 名患者的 57 个预测的人类白细胞抗原（HLA）-A*02:01 结合表位中的 11 个。许多 T 细胞反应涉及到体内被患者自体肿瘤浸润淋巴细胞忽视的表位。最后，用从供体衍生的 T 细胞中鉴定出的 T 细胞受体重定向的 T 细胞有效地识别了携带相关突变的患者来源的黑色素瘤细胞，为在癌症免疫治疗中使用这种“外包”免疫反应提供了依据。
