Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors

被引:9
|
作者
Shida, Yoichi [1 ]
Nakazawa, Tsutomu [1 ,2 ]
Matsuda, Ryosuke [1 ]
Morimoto, Takayuki [1 ]
Nishimura, Fumihiko [1 ]
Nakamura, Mitsutoshi [1 ,3 ]
Maeoka, Ryosuke [1 ]
Yamada, Shuichi [1 ]
Nakagawa, Ichiro [1 ]
Park, Young-Soo [1 ]
Yasukawa, Motoaki [4 ,5 ]
Tojo, Takashi [4 ,6 ]
Tsujimura, Takahiro [3 ]
Nakase, Hiroyuki [1 ]
机构
[1] Nara Med Univ, Dept Neurosurg, Kashihara, Nara 6348521, Japan
[2] Grandsoul Res Inst Immunol Inc, Uda, Nara 6332221, Japan
[3] Clin Grandsoul Nara, Uda, Nara 6332221, Japan
[4] Nara Med Univ, Dept Thorac Surg, Kashihara, Nara 6348521, Japan
[5] Osaka Kaisei Hosp, Dept Surg, Yodogawa, Osaka 5320003, Japan
[6] Saiseikai Chuwa Hosp, Dept Thorac Surg, Sakurai, Nara 6330054, Japan
关键词
PD-1; PD-L1; NK cell; glioblastoma; NEWLY-DIAGNOSED GLIOBLASTOMA; DELTA-T CELLS; ADJUVANT TEMOZOLOMIDE; PD-L1; EXPRESSION; NK CELLS; IMMUNOTHERAPY; THERAPY; RADIOTHERAPY; CONCOMITANT; PATTERNS;
D O I
10.3390/ijms22189975
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glioblastoma (GBM) is the leading malignant intracranial tumor and is associated with a poor prognosis. Highly purified, activated natural killer (NK) cells, designated as genuine induced NK cells (GiNKs), represent a promising immunotherapy for GBM. We evaluated the anti-tumor effect of GiNKs in association with the programmed death 1(PD-1)/PD-ligand 1 (PD-L1) immune checkpoint pathway. We determined the level of PD-1 expression, a receptor known to down-regulate the immune response against malignancy, on GiNKs. PD-L1 expression on glioma cell lines (GBM-like cell line U87MG, and GBM cell line T98G) was also determined. To evaluate the anti-tumor activity of GiNKs in vivo, we used a xenograft model of subcutaneously implanted U87MG cells in immunocompromised NOG mice. The GiNKs expressed very low levels of PD-1. Although PD-L1 was expressed on U87MG and T98G cells, the expression levels were highly variable. Our xenograft model revealed that the retro-orbital administration of GiNKs and interleukin-2 (IL-2) prolonged the survival of NOG mice bearing subcutaneous U87MG-derived tumors. PD-1 blocking antibodies did not have an additive effect with GiNKs for prolonging survival. GiNKs may represent a promising cell-based immunotherapy for patients with GBM and are minimally affected by the PD-1/PD-L1 immune evasion axis in GBM.
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页数:14
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