Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors.
Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors.
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DOI：
10.1186/s40425-016-0164-7
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发表时间：
2016
影响因子：
10.9
通讯作者：
Sarnaik AA
中科院分区：
文献类型：
--
作者：
Hall M;Liu H;Malafa M;Centeno B;Hodul PJ;Pimiento J;Pilon-Thomas S;Sarnaik AA
我们评估了肿瘤浸润性淋巴细胞(TIL)是否可以从胰腺癌患者手术切除的肿瘤中扩增。肿瘤切除自胰腺癌患者。将肿瘤切成碎片，在含有高剂量白介素2(IL-2)的培养液中培养长达6周。检测T细胞表型、活化标志物和反应性。对19例患者的TIL扩张进行了测量。这些TIL中大部分是CD4+T细胞，并且高度活化。纯化的CD8+T细胞产生干扰素-γ，以应答与人类白细胞抗原相匹配的胰腺肿瘤靶点。PD-1阻断和4-1BB刺激被证明是提高有效TIL产量的有效策略，包括产生肿瘤反应性胰腺TIL。从胰腺肿瘤中扩增出来的TIL具有一定的功能，能够对胰腺肿瘤相关抗原产生应答。阻断PD-1、41BB刺激、CD8+T细胞浓缩是提高TIL产量和肿瘤反应性的有效策略。这些结果支持了使用TIL治疗胰腺癌的过继细胞治疗策略的发展。本文的在线版本(doi：10.1186/s40425-016-0164-7)包含补充材料，授权用户可以使用。
We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients. Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured. TIL expansion was measured in 19 patient samples. The majority of these TIL were CD4+ T cells and were highly activated. Purified CD8+ T cells produced IFN-γ in response to HLA-matched pancreatic tumor targets. PD-1 blockade and 4-1BB stimulation were demonstrated as effective strategies to improve effective TIL yield, including the production of tumor-reactive pancreatic TIL. TIL expanded from pancreatic tumors are functional and able to respond to pancreatic tumor associated antigens. PD-1 blockade, 41BB stimulation, and CD8+ T cell enrichment are effective strategies to improve TIL yield and tumor reactivity. These results support the development of adoptive cell therapy strategies using TIL for the treatment of pancreatic cancer. The online version of this article (doi:10.1186/s40425-016-0164-7) contains supplementary material, which is available to authorized users.
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影响因子：
8.8
作者：
Ino Y;Yamazaki-Itoh R;Shimada K;Iwasaki M;Kosuge T;Kanai Y;Hiraoka N
通讯作者：
Hiraoka N
DOI：
10.1084/jem.20101876
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
De Monte L;Reni M;Tassi E;Clavenna D;Papa I;Recalde H;Braga M;Di Carlo V;Doglioni C;Protti MP
通讯作者：
Protti MP
DOI：
10.1097/cji.0b013e3181fad2b0
发表时间：
2010-11
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Inozume T;Hanada K;Wang QJ;Ahmadzadeh M;Wunderlich JR;Rosenberg SA;Yang JC
通讯作者：
Yang JC
DOI：
10.1158/1078-0432.ccr-10-1297
发表时间：
2010-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dudley ME;Gross CA;Langhan MM;Garcia MR;Sherry RM;Yang JC;Phan GQ;Kammula US;Hughes MS;Citrin DE;Restifo NP;Wunderlich JR;Prieto PA;Hong JJ;Langan RC;Zlott DA;Morton KE;White DE;Laurencot CM;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
10.1
作者：
Lutz ER;Wu AA;Bigelow E;Sharma R;Mo G;Soares K;Solt S;Dorman A;Wamwea A;Yager A;Laheru D;Wolfgang CL;Wang J;Hruban RH;Anders RA;Jaffee EM;Zheng L
通讯作者：
Zheng L