ABSTRACT

Background

Cancer immunotherapies have achieved much success and have become the forefront treatment of cancers previously associated with poor prognosis. However, a major challenge in cancer immunotherapies remains the heterogeneity of the immunoregulatory capacities of cancers, and not all patients of a given cancer responds to current therapeutic strategies. To address this issue and to facilitate the development of new pharmacological compounds, we here describe an in vitro model of dendritic cell suppression by cancer cells.

Methods

We treated monocyte-derived dendritic cells with conditioned medium from cancer cell lines and assessed their maturation using ELISA and flow cytometry. In addition, we assessed their ability to induce T cell activation and differentiation.

Results

We found that both the phenotypic and functional maturation of dendritic cells was suppressed by the conditioned medium. The expression of IL-12p70, TNF-α, CD80, CD83, and CD86 was significantly reduced by conditioned medium from the 786-O and HeLa cell lines, and CD4⁺ T cells had a weaker T_H1 phenotype with significantly decreased expression of IFN-γ and T-bet following co-culturing. Furthermore, we use our model to characterize the differential immunoregulatory capacities of primary cancers by using conditioned medium of cultured primary cancer cells.

Conclusion

This model can be used to screen pharmacological compounds seeking to alleviate the immunosuppression of the tumor microenvironment and can furthermore be used to investigate the immunoregulatory capacities of primary cancer cells, which could be a helpful prognostic tool following tumor resection.

中文翻译：

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开发评估药理化合物和逆转肿瘤源性树突状细胞免疫抑制的体外测定法

摘要

背景

癌症免疫疗法已经取得了很大的成功，并已成为以前与预后不良相关的癌症的前沿治疗方法。然而，癌症免疫疗法的主要挑战仍然是癌症免疫调节能力的异质性，并且并非所有特定癌症的患者都对当前的治疗策略有反应。为了解决这个问题并促进新药理化合物的开发，我们在这里描述了癌细胞抑制树突状细胞的体外模型。

方法

我们用来自癌细胞系的条件培养基处理单核细胞衍生的树突状细胞，并使用 ELISA 和流式细胞术评估它们的成熟度。此外，我们评估了它们诱导 T 细胞活化和分化的能力。

结果

我们发现条件培养基抑制了树突状细胞的表型成熟和功能成熟。来自 786-O 和 HeLa 细胞系的条件培养基显着降低了 IL-12p70、TNF-α、CD80、CD83 和 CD86 的表达，并且 CD4 ⁺ T 细胞具有较弱的 T _H 1 表型，其表达显着降低共培养后的 IFN-γ 和 T-bet。此外，我们使用我们的模型通过使用培养的原发性癌细胞的条件培养基来表征原发性癌症的差异免疫调节能力。

结论

该模型可用于筛选旨在减轻肿瘤微环境免疫抑制的药理学化合物，还可用于研究原发性癌细胞的免疫调节能力，这可能是肿瘤切除后有用的预后工具。