Phenotypic and Functional Characteristics of CD8+ T Cells Predict Clinical Outcome Following TIL Therapy in a Randomized Phase III Trial in Advanced Melanoma.

In the randomized phase III clinical trial [TIL-Netherlands Cancer Institute (NKI)/National Center for Cancer Immune Therapy (CCIT)], TIL therapy significantly improved progression-free survival(PFS) compared with ipilimumab in patients with unresectable stage IIIC and IV cutaneous melanoma.

在随机III期临床试验[TIL-荷兰癌症研究所(NKI)/国家癌症免疫治疗中心(CCIT)]中，与伊匹木单抗相比，TIL疗法显著改善了不可切除的IIIC期和IV期皮肤黑色素瘤患者的无进展生存期(PFS)。

This study aimed to define the phenotypic and functional characteristics of the infused TIL associated with the best overall response (BOR) and PFS.

本研究旨在明确与最佳总反应（BOR）和无进展生存期（PFS）相关的输注肿瘤浸润淋巴细胞（TIL）的表型和功能特征。

experimental_design

Using flow cytometry, we profiled infusion products from all 80 patients treated with TILs in the TIL-NKI/CCIT trial and correlated the results with BOR and PFS.

我们使用流式细胞术分析了TIL-NKI/CCIT试验中所有80名接受TIL治疗患者的输注产品，并将结果与BOR和PFS进行了相关性分析。

We established autologous tumor cell lines from 24 patients and assessed the antitumor reactivity of the infused CD4+ and CD8+ T cells through coculture assays and intracellular cytokine staining.

我们从24名患者中建立了自体肿瘤细胞系，并通过共培养实验和细胞内细胞因子染色评估了输注的CD4+和CD8+ T细胞的抗肿瘤反应性。

We quantified tumor-reactive TILs relative to baseline tumor volume and monitored their persistence in the peripheral blood for up to 24 months after infusion.

我们根据基线肿瘤体积量化了肿瘤反应性TILs，并监测了它们在输注后长达24个月在周围血中的持续性。

Results

Responding patients received a higher absolute number of CD8+TCRαβ+ T cells than nonresponders (P = 0.0290).

反应良好的患者接受的CD8+TCRαβ+ T细胞的绝对数量高于无反应者（P = 0.0290）。

The frequency of infusion product CD8+TCRαβ+ T cells was strongly associated with PFS at 6 months (P < 0.0001).

输注产品中CD8+TCRαβ+ T细胞的频率与6个月无进展生存期（PFS）有很强的相关性（P < 0.0001）。

The number of tumor-reactive CD8+ T cells infused, normalized to baseline tumor burden, correlated with BOR (P = 0.0352) and PFS at 6 months (P = 0.0007), with sustained peripheral blood persistence of tumor-reactive CD4+ and CD8+ T cells predictive of durable clinical response.

输注的肿瘤反应性 CD8+ T 细胞数量，根据基线肿瘤负担进行标准化，与 BOR (P = 0.0352) 和 6 个月的 PFS (P = 0.0007) 相关，肿瘤反应性 CD4+ 和 CD8+ T 细胞在外周血中的持续存在预示着持久的临床反应。

Conclusions

CD8+ T-cell phenotype, tumor reactivity, and in vivo persistence emerged as strong predictors of clinical outcome.

CD8+ T 细胞表型、肿瘤反应性和体内持续性成为临床结果的强有力的预测因素。

Our data identify CD8+ T cells as a key determinant of therapeutic efficacy.

我们的数据将CD8+ T细胞确定为治疗效果的关键决定因素。