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

Junko Johansson; Jan Siarov; Roberta Kiffin; Johan Mölne; Jan Mattsson; Peter Naredi; Roger Olofsson Bagge; Anna Martner; Per Lindnér

doi:10.1080/2162402X.2020.1854519

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.

Authors

Junko Johansson^{1

2

3}, Jan Siarov⁴, Roberta Kiffin^{5

6}, Johan Mölne⁴, Jan Mattsson², Peter Naredi^{1

2}, Roger Olofsson Bagge^{1

2

3}, Anna Martner^{5

6}, Per Lindnér^{1

7}

Affiliations

¹ Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
³ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ TIMM Laboratory, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷ Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.

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

Grants and funding

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].