Modulation of the Human Pancreatic Ductal Adenocarcinoma Immune Microenvironment by Stereotactic Body Radiotherapy

被引:41
作者
Mills, Bradley N. [1 ]
Qiu, Haoming [2 ,3 ]
Drage, Michael G. [4 ]
Chen, Chunmo [4 ]
Mathew, Jocelyn S. [1 ]
Garrett-Larsen, Jesse [1 ]
Ye, Jian [1 ]
Uccello, Taylor P. [5 ]
Murphy, Joseph D. [5 ]
Belt, Brian A. [1 ]
Lord, Edith M. [3 ,5 ]
Katz, Alan W. [2 ,3 ]
Linehan, David C. [1 ,3 ]
Gerber, Scott A. [1 ,3 ,5 ]
机构
[1] Univ Rochester, Dept Surg, Med Ctr, 601 Elmwood Ave, Rochester, NY 14642 USA
[2] Univ Rochester, Dept Radiat Oncol, Med Ctr, Rochester, NY 14642 USA
[3] Univ Rochester, Wilmot Canc Inst, Med Ctr, Rochester, NY 14642 USA
[4] Univ Rochester, Dept Pathol & Lab Med, Med Ctr, Rochester, NY 14642 USA
[5] Univ Rochester, Dept Microbiol & Immunol, Med Ctr, Rochester, NY 14642 USA
关键词
RADIATION-THERAPY; TUMOR MICROENVIRONMENT; CELL-DEATH; BLOCKADE; CANCER; EXPRESSION; SIGNATURES; APOPTOSIS; RADIOSURGERY; MACROPHAGES;
D O I
10.1158/1078-0432.CCR-21-2495
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC), which can effectively prime cytotoxic T cells by inducing immu-nogenic tumor cell death in preclinical models. SBRT effects on human PDAC have yet to be thoroughly investigated; therefore, this study aimed to characterize immunomodulation in the human PDAC tumor microenvironment following therapy. Experimental Design: Tumor samples were obtained from patients with resectable PDAC. Radiotherapy was delivered a median of 7 days prior to surgical resection, and sections were analyzed by multiplex IHC (mIHC), RNA sequencing, and T-cell receptor sequencing (TCR-seq). Results: Analysis of SBRT-treated tumor tissue indicated reduced tumor cell density and increased immunogenic cell
引用
收藏
页码:150 / 162
页数:13
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