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

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.