The impairment of CD3+ T lymphocytes in sentinel lymph node of high-risk cutaneous melanoma patients in stage IIB and IIC.

BACKGROUND

The sentinel lymph node (SLN) in melanoma is almost always the first site of metastasis and its histopathological assessment is essential for the determination of staging and clinical outcome. Furthermore, this procedure offers the investigation of the early immune response in SLN as melanoma-derived factors suppress the immunity in an early stage that may facilitate metastasis. A better understanding of the immunological changes in SLN may help in the therapeutic stimulation of melanoma immunity to prevent tumor metastasis.

METHODS

SLN tissues without malignant cells from 74 cutaneous melanoma patients (stage I and II) were analyzed. By flow cytometry, we measured the percentage of natural killer cells, CD3+ T lymphocytes, and their expression of interferon-γ (IFN-γ) and inhibitory immune checkpoint molecules (ICMs), and the percentage of CD4+Foxp3+ regulatory T cells (Tregs).

RESULTS

Melanoma patients with worse prognosis, in stage IIB-C, had decreased percentage of total CD3+ and CD3+CD8+ T lymphocytes, trend of IFN-γ decrease, increased inhibitory programmed cell death 1 and T cell immunoglobulin and mucin-domain containing 3 ICMs, and higher percentage of Tregs in their SLNs compared with stage I-IIA patients. Furthermore, patients with nodular melanoma had decreased CD3+CD8+ cells compared with patients with superficial spreading melanoma and together with patients with localization of primary tumor on extremities had an increase in the expression of analyzed ICMs.

CONCLUSIONS

This study provides new results of the impairment of immune response in SLN of cutaneous melanoma patients with high risk for metastasis and could help in the introduction of new immunotherapies that could restore immunity and prevent metastasis in SLN.