Antigen-Driven T-Cell Selection in Patients with Cervical Cancer as Evidenced by T-Cell Receptor Analysis and Recognition of Autologous Tumor

H. Pilch; H. H?hn; C. Neukirch; K. Freitag; P. G. Knapstein; B. Tanner

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Antigen-Driven T-Cell Selection in Patients with Cervical Cancer as Evidenced by T-Cell Receptor Analysis and Recognition of Autologous Tumor

机译：通过T细胞受体分析和自体肿瘤识别证明宫颈癌患者的抗原驱动T细胞选择

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We characterized the T-cell receptor (TCR) repertoire in freshly harvested tumor lesions, in short-term-expanded CD4+ tumor infiltrating lymphocytes (TIL) as well as in CD4+ and CD8+ peripheral blood lymphocytes (PBL) from three patients with cervical cancer. Skewing of the T-cell repertoire as defined by measuring the length of the complementarity-determining region 3 (CDR3) of the TCR VA and VB chains was observed in CD8+ PBL, in freshly harvested tumor tissue, as well as in CD4+ TIL. Comparative analysis of the TCR repertoire revealed unique monoclonal TCR transcripts within the tumor lesion which were not present in PBL, suggesting selection of TCR clonotypes due to antigenic stimulation. TCR repertoire analysis of the short-term (7-day) CD4+ TIL lines revealed that the TCR composition is markedly different from that in CD4+ PBL or in the freshly harvested tumor tissue. Only one-third of CD4+ TIL lines showed HLA-DR-restricted recognition of autologous tumor cells as defined by cytolysis. These data provide support for the antigen-driven selection of T cells within cervical cancer lesions and suggest that analysis of the TCR repertoire may aid in obtaining an objective description of the immune response in patients with cervical cancer who are undergoing epitope-based immunotherapy.

机译：我们在新近收获的肿瘤病变，短期扩增的CD4 + 肿瘤浸润淋巴细胞（TIL）和CD4 + 和CD8 + 外周血淋巴细胞（PBL）。在新鲜收获的肿瘤组织中，在CD8 + PBL中观察到通过测量TCR VA和VB链的互补决定区3（CDR3）的长度定义的T细胞库的倾斜，以及CD4 + TIL中的内容。对TCR库的比较分析揭示了肿瘤病变内独特的单克隆TCR转录物，其在PBL中不存在，表明由于抗原刺激而选择了TCR克隆型。对短期（7天）CD4 + TIL品系的TCR库分析表明，TCR组成与CD4 + PBL或新鲜收获的TCL组成明显不同肿瘤组织。 CD4 + TIL系中只有三分之一表现出HLA-DR限制的对自体肿瘤细胞的识别，如细胞溶解所定义的。这些数据为抗原驱动的子宫颈癌病变内T细胞的选择提供了支持，并建议对TCR库的分析可能有助于获得正在接受基于表位免疫治疗的子宫颈癌患者的免疫应答的客观描述。

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《Clinical and diagnostic laboratory immunology》 |2002年第2期|共12页
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H. Pilch; H. H?hn; C. Neukirch; K. Freitag; P. G. Knapstein; B. Tanner;
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1. Antigen-Driven T-Cell Selection in Patients with Cervical Cancer as Evidenced by T-Cell Receptor Analysis and Recognition of Autologous Tumor [J] . H. Pilch, H. H?hn, C. Neukirch, Clinical and diagnostic laboratory immunology . 2002,第2期

机译：通过T细胞受体分析和自体肿瘤识别证明宫颈癌患者的抗原驱动T细胞选择
2. Dominant responses with conservation of T-cell receptor usage in the CD8+ T-cell recognition of a cancer testis antigen peptide presented through HLA-Cw7 in patients with multiple myeloma [J] . GoodyearO.C., PearceH., PrattG., Cancer immunology, immunotherapy : . 2011,第12期

机译：多发性骨髓瘤患者通过HLA-Cw7呈递的CD8 + T细胞识别的睾丸抗原肽的T细胞受体使用的保守应答
3. Dominant responses with conservation of T-cell receptor usage in the CD8+ T-cell recognition of a cancer testis antigen peptide presented through HLA-Cw7 in patients with multiple myeloma [J] . Oliver C. Goodyear, Hayden Pearce, Guy Pratt, Cancer Immunology, Immunotherapy . 2011,第12期

机译：多发性骨髓瘤患者通过HLA-Cw7呈递的CD8 + T细胞识别癌睾丸抗原肽的T细胞受体使用的保守应答
4. Engineering and Arming of Soluble T-Cell Receptors for Targeting of Tumor Specific HLA Ligands [C] . Dominik Maurer Protein Engineering Summit. . 2018

机译：肿瘤特异性HLA配体靶向可溶性T细胞受体的工程与武装
5. Analysis of supernumerary clonal gamma T-cell receptor gene rearrangements in cutaneous T-cell lymphoma [D] . Tolpinrud, Whitney Lynn 2011

机译：皮肤T细胞淋巴瘤中叠加克隆γT细胞受体基因重排分析
6. Antigen-Driven T-Cell Selection in Patients with Cervical Cancer as Evidenced by T-Cell Receptor Analysis and Recognition of Autologous Tumor [O] . H. Pilch, H. Höhn, C. Neukirch, 2002

机译：通过T细胞受体分析和自体肿瘤识别证明宫颈癌患者的抗原驱动T细胞选择
7. Antigen-Driven T-Cell Selection in Patients with Cervical Cancer as Evidenced by T-Cell Receptor Analysis and Recognition of Autologous Tumor [O] . Pilch, H., Höhn, H., Neukirch, C., 2002

机译：通过T细胞受体分析和自体肿瘤识别证明宫颈癌患者的抗原驱动T细胞选择
8. Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity [R] . Gray, A. 2011

机译：通过操纵T细胞受体信号增强前列腺癌免疫治疗的功效，以改变外周调节性T细胞活性

Antigen-Driven T-Cell Selection in Patients with Cervical Cancer as Evidenced by T-Cell Receptor Analysis and Recognition of Autologous Tumor

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