TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

被引：56

作者：

Hsu, Melody S. ^{[1
,2
]}

Sedighim, Shaina ^{[1
]}

Wang, Tina ^{[1
,3
]}

Antonios, Joseph P. ^{[1
,4
]}

Everson, Richard G. ^{[1
]}

Tucker, Alexander M. ^{[1
]}

Du, Lin ^{[5
]}

Emerson, Ryan ^{[6
]}

Yusko, Erik ^{[6
]}

Sanders, Catherine ^{[6
]}

Robins, Harlan S. ^{[6
,7
]}

Yong, William H. ^{[8
,9
]}

Davidson, Tom B. ^{[1
,2
,8
]}

Li, Gang ^{[5
,8
]}

Liau, Linda M. ^{[1
,8
]}

Prins, Robert M. ^{[1
,8
,10
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, 300 Stein Plaza,Suite 562,Box 956901, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Hematol Oncol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Med Scientist Training Program, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA

[6] Adapt Biotechnol, Seattle, WA USA

[7] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[8] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA

[9] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA

[10] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, David Geffen Sch Med, Los Angeles, CA 90095 USA

来源：

CANCER IMMUNOLOGY RESEARCH | 2016年 / 4卷 / 05期

关键词：

GLIOBLASTOMA; LYMPHOCYTES; BROADENS; THERAPY;

D O I：

10.1158/2326-6066.CIR-15-0240

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Although immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next-generation sequencing approach to determine whether quantitative assessments of tumor-infiltrating lymphocyte (TIL) content and the degree of overlap of T-cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma patients treated with autologous tumor lysate-pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune (C) 2016 AACR.

引用

页码：412 / 418

页数：7

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