Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients

特定淋巴细胞亚群可预测转移性黑色素瘤患者对使用扩增自体肿瘤浸润淋巴细胞进行的过继细胞疗法的反应

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作者:Laszlo G Radvanyi, Chantale Bernatchez, Minying Zhang, Patricia S Fox, Priscilla Miller, Jessica Chacon, Richard Wu, Gregory Lizee, Sandy Mahoney, Gladys Alvarado, Michelle Glass, Valen E Johnson, John D McMannis, Elizabeth Shpall, Victor Prieto, Nicholas Papadopoulos, Kevin Kim, Jade Homsi, Agop Be

Conclusion

These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8(+) T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression.

Purpose

Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the

Results

Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8(+) T cells in the infusion product, a more differentiated effector phenotype of the CD8(+) population, and a higher frequency of CD8(+) T cells coexpressing the negative costimulation molecule "B- and T-lymphocyte attenuator" (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified.

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