黑色素瘤的短期和长期免疫抑制作用会影响前哨淋巴结状态的预后价值。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2024-10-04 DOI:10.1016/j.ejca.2024.115054

Viola K. DeTemple , Cathrin Ritter , Nalini Srinivas , Ivelina Spassova , Thilo Gambichler , Svea Hüning , Nikolai Gräger , Ralf Gutzmer , Eva-Bettina Bröcker , Selma Ugurel , David Schrama , Jürgen C. Becker

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引用次数: 0

摘要

背景：前哨淋巴结（SLN）是否存在微转移目前被用于评估黑色素瘤患者的预后。目的：我们研究了原发肿瘤（PT）对前哨淋巴结（SLN）免疫学影响的时间依赖性和内在机制：方法：我们评估了SLN状态作为PT切除时间函数的预后价值。为了将结果置于功能背景下，对选定的PT和相应的SLN进行了基因和蛋白质表达模式分析：结果：在202例已知有远处转移且PT预后特征相似的患者队列中，PT切除前或切除后一周内切除的SLN（IM-SLN）比PT切除后至少一周内切除的SLN（DEL-SLN）有更高的微转移发生率。研究发现，IM-SLN 的免疫活性低于 DEL-SLN。具体来说，在IM-SLN中，T辅助细胞17/调节性T细胞占主导地位，而在DEL-SLN中，细胞毒性γδT细胞更为常见。DEL-SLNs中较高的免疫活性可能是由CD209+抗原递呈细胞促成的。事实上，在TGFβ高表达的PT中，CD209+细胞似乎被困住了，在DEL-SLN中没有观察到免疫活性增加：结论：DEL-SLN 中存在微转移灶与 IM-SLN 中存在微转移灶相比，具有更高的负面预后价值，因为微转移灶不仅表明黑色素瘤具有转移倾向，还可能表明黑色素瘤具有逃避免疫反应的能力。

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Short- and long-term immunosuppressive effects of melanoma influence the prognostic value of the sentinel lymph node status

Background

Presence of micrometastases in the sentinel lymph node (SLN) is currently used to assess prognosis of melanoma patients. The immunoactivity within the SLN is known to be influenced by the primary tumor (PT), which may in turn impact the SLNs’ metastatic state.

Aim

We characterize the temporal dependence and underlying mechanisms of the immunological effects of the PT on the SLN.

Methods

The prognostic value of SLN state as a function of PT removal time was evaluated. To put the results into a functional context, selected PTs and corresponding SLNs were analyzed for gene and protein expression patterns.

Results

In a cohort of 202 patients with known distant metastasis and similar PT prognostic characteristics, SLNs removed before or within one week after the PT (IM-SLN) had a higher incidence of micrometastases than those removed at least one week after the PT (DEL-SLN).

The immunoactivity in IM-SLN was found to be lower than in DEL-SLN. Specifically, in IM-SLNs, T helper 17 / regulatory T-cells were predominant, whereas in DEL-SLNs, cytotoxic γδT-cells were more frequent. The higher immune activity in DEL-SLNs was probably facilitated by CD209⁺ antigen-presenting cells. Indeed, in PT with high TGFβ expression CD209⁺ cells appear to be trapped and no increased immunoactivity was observed in DEL-SLN.

Conclusions

Presence of micrometastases in DEL-SLNs have a higher negative prognostic value as in IM-SLNs since they indicate not only a melanoma’s propensity to metastasize, but possibly also its capacity to escape immune responses.

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

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