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

Eur J Cancer

Department of Translational Skin Cancer Research (TSCR), German Cancer Consortium (DKTK), partner site Essen, University Duisburg-Essen, Universitätsstr. 1, 45141 Essen, Germany; Department of Dermatology, University Medicine Essen, Hufelandstraße 55, 45147 Essen, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address:

Published: November 2024

AI Article Synopsis

  • The study investigates the effects of primary tumor (PT) on the immune activity and metastatic status of sentinel lymph nodes (SLNs) in melanoma patients.
  • It finds that SLNs removed shortly after PT (IM-SLNs) show a higher incidence of micrometastases and lower immune activity compared to those removed later (DEL-SLNs).
  • Higher immune activity and the presence of specific immune cells in DEL-SLNs suggest that the timing of SLN removal influences prognosis, with DEL-SLNs indicating a worse outcome due to the melanoma's ability to evade immune responses.

Article Abstract

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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http://dx.doi.org/10.1016/j.ejca.2024.115054DOI Listing

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