Presence of tumor-infiltrating CD8 + T cells and macrophages correlates to longer overall survival in patients undergoing isolated hepatic perfusion for uveal melanoma liver metastasis

Oncoimmunology. 2020 Dec 10;9(1):1854519. doi: 10.1080/2162402X.2020.1854519.

Abstract

Uveal melanoma is a malignant tumor of the eye that often metastasizes to the liver conferring poor prognosis. When comparing immune profiles in peripheral blood of untreated patients with uveal melanoma liver metastasis and healthy blood donors, it was observed that immune cells of uveal melanoma patients carried immunosuppressive features. Patient blood contained an increased content of CD14+HLA-DR-/low M-MDSCs and inflammatory CD16+ monocytes, while their dendritic cells expressed lower levels of activation markers. Melanoma patients also harbored an enhanced fraction of CD4+Foxp3+ regulatory T cells, while their effector T cells expressed lower levels of the activation marker HLA-DR. Biopsies from liver metastases were obtained from patients with uveal melanoma that subsequently underwent hyperthermic isolated hepatic perfusion (IHP) with melphalan. There were trends indicating a positive correlation between a high infiltration of CD8+ T cells in metastases and an activated immune cell profile in blood. High metastatic infiltration of CD8+ T cells and CD68+ macrophages, but not of immunosuppressive CD163+ macrophages, correlated to a longer overall survival in patients treated with IHP. Hence, while the immune system of patients with uveal melanoma shows signs of immunosuppression, the presence of activated immune cells may correlate to a longer survival, at least following IHP treatment.

Keywords: CD68+; CD8+; T cells; Uveal melanoma; isolated hepatic perfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Humans
  • Liver Neoplasms* / drug therapy
  • Macrophages
  • Melanoma* / drug therapy
  • Perfusion
  • Uveal Neoplasms* / drug therapy

Supplementary concepts

  • Uveal melanoma

Grant support

This work was supported by the Cancerfonden [CAN 2016/351 19 0033 Pj]; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden; The Agreement for Medical Education and Research [ALFGBG-724881]; Stiftelsen Assar Gabrielssons Fond [FB18-15]; Vetenskapsrådet [2016-01928].