从人胰腺肿瘤中扩增肿瘤浸润淋巴细胞（TIL）。
Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors.
机构信息
Department of Immunology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
Gastrointestinal Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
出版信息
J Immunother Cancer. 2016 Oct 18;4:61. doi: 10.1186/s40425-016-0164-7. eCollection 2016.
BACKGROUND
We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
背景
我们评估了是否可以从胰腺癌患者手术切除的肿瘤中扩增肿瘤浸润淋巴细胞（TIL）。
方法
从胰腺癌患者中切除肿瘤。将肿瘤切成碎片，并在含有高剂量白细胞介素 2（IL-2）的培养基中培养长达 6 周。测量 T 细胞表型、激活标志物和反应性。
结果
在 19 个患者样本中测量了 TIL 的扩增。这些 TIL 大多数是 CD4 T 细胞，并且高度激活。纯化的 CD8 T 细胞在对 HLA 匹配的胰腺肿瘤靶标作出反应时产生 IFN-γ。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，包括产生针对胰腺肿瘤的 TIL。
结论
从胰腺肿瘤中扩增的 TIL 是功能性的，能够对胰腺肿瘤相关抗原作出反应。PD-1 阻断、41BB 刺激和 CD8 T 细胞富集是提高 TIL 产量和肿瘤反应性的有效策略。这些结果支持使用 TIL 开发过继细胞治疗策略来治疗胰腺癌。
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