Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer.
Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer.
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DOI：
10.18632/oncotarget.23007
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发表时间：
2017-12-26
期刊：
影响因子：
--
通讯作者：
Gong G
中科院分区：
文献类型：
--
作者：
Lee HJ;Kim YA;Sim CK;Heo SH;Song IH;Park HS;Park SY;Bang WS;Park IA;Lee M;Lee JH;Cho YS;Chang S;Jung J;Kim J;Lee SB;Kim SY;Lee MS;Gong G
体外扩增的肿瘤浸润淋巴细胞（TIL）的连续细胞转移（ACT）已成功治疗相当大比例的转移性黑色素瘤患者。此外，最近有报道称，一些患有其他几种实体瘤的患者在临床上从ACT中获益。然而，目前尚不清楚使用TIL的ACT是否广泛适用于乳腺癌，这是女性最常见的癌症。在这项研究中，TILs作为ACT来源在乳腺癌中的效用进行了探索，从大量的乳腺癌样本中获得TILs，并评估其生物学潜力。我们在标准TIL培养条件下成功地从100多个乳腺癌样品中体外扩增了TIL，包括所有乳腺癌亚型。我们还发现，有关肿瘤组织中TIL的百分比和三级淋巴样结构的存在的信息可用于估计离体培养后可获得的TIL的数量。体外扩增的TIL含有相当水平的中央记忆表型T细胞（约20%），并且大比例的TIL样品在体外对自体肿瘤细胞具有反应性。此外，体外肿瘤反应性自体TIL也可以在植入原发性肿瘤组织的异种移植小鼠模型中体内发挥作用。总的来说，这些结果强烈表明，使用离体扩增的自体TIL的ACT是治疗乳腺癌患者的可行选择。
Adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) has been successful in treating a considerable proportion of patients with metastatic melanoma. In addition, some patients with several other solid tumors were recently reported to have benefited clinically from such ACT. However, it remains unclear whether ACT using TILs is broadly applicable in breast cancer, the most common cancer in women. In this study, the utility of TILs as an ACT source in breast cancers was explored by deriving TILs from a large number of breast cancer samples and assessing their biological potentials. We successfully expanded TILs ex vivo under a standard TIL culture condition from over 100 breast cancer samples, including all breast cancer subtypes. We also found that the information about the percentage of TIL and presence of tertiary lymphoid structure in the tumor tissues could be useful for estimating the number of obtainable TILs after ex vivo culture. The ex vivo expanded TILs contained a considerable level of central memory phenotype T cells (about 20%), and a large proportion of TIL samples were reactive to autologous tumor cells in vitro. Furthermore, the in vitro tumor-reactive autologous TILs could also function in vivo in a xenograft mouse model implanted with the primary tumor tissue. Collectively, these results strongly indicate that ACT using ex vivo expanded autologous TILs is a feasible option in treating patients with breast cancer.
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影响因子：
8.8
作者：
Baldan, V.;Griffiths, R.;Hawkins, R. E.;Gilham, D. E.
通讯作者：
Gilham, D. E.
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
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影响因子：
11.5
作者：
Besser, Michal J.;Shapira-Frommer, Ronnie;Schachter, Jacob
通讯作者：
Schachter, Jacob
影响因子：
10.1
作者：
Harao M;Forget MA;Roszik J;Gao H;Babiera GV;Krishnamurthy S;Chacon JA;Li S;Mittendorf EA;DeSnyder SM;Rockwood KF;Bernatchez C;Ueno NT;Radvanyi LG;Vence L;Haymaker C;Reuben JM
通讯作者：
Reuben JM
影响因子：
45.3
作者：
Liedtke, Cornelia;Mazouni, Chafika;Pusztai, Lajos
通讯作者：
Pusztai, Lajos