Oncotarget

Research Papers:

Characterization of infiltrating lymphocytes in human benign and malignant prostate tissue

Emelie Rådestad _, Lars Egevad, Carl Jorns, Jonas Mattsson, Berit Sundberg, Silvia Nava, Bo-Göran Ericzon, Lars Henningsohn, Victor Levitsky and Michael Uhlin

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Oncotarget. 2017; 8:60257-60269. https://doi.org/10.18632/oncotarget.19528

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Abstract

Emelie Rådestad1, Lars Egevad2,3, Carl Jorns1, Jonas Mattsson2,4, Berit Sundberg2, Silvia Nava1, Bo-Göran Ericzon1, Lars Henningsohn1,5, Victor Levitsky6 and Michael Uhlin1,7,8

1Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

2Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

3Department of Pathology, Karolinska University Hospital, Stockholm, Sweden

4Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden

5Department of Urology, Karolinska University Hospital, Stockholm, Sweden

6Molecular Partners AG, Schlieren-Zurich, Switzerland

7Department of Immunology/Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden

8Department of Applied Physics, Royal Institute of Technology, Stockholm, Sweden

Correspondence to:

Emelie Rådestad, email: [email protected]

Keywords: prostate cancer, benign prostatic hyperplasia, prostate-infiltrating lymphocytes, checkpoint blockade, PD-1

Received: February 28, 2017     Accepted: July 18, 2017     Published: July 24, 2017

ABSTRACT

Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8+ and had a CCR7CD45RO+ effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates. Furthermore, there were differences between the prostate conditions regarding the percentage of T-cells expressing several activation markers and co-inhibitory receptors. In conclusion, many prostate-infiltrating T-cells express co-inhibitory receptors PD-1 and LAG-3, regardless of prostate condition. Despite the observed increase in counts and percentages of PD-1+ T-cells in PC, the concomitant demonstration of high percentage of PD-1+ T-cells in control prostates suggests that PD-1 may play a role in controlling the homeostasis of the prostate rather than in contributing to PC-associated immune-suppression. Thus, PD-1 may not be a good candidate for checkpoint blockade in PC and these data are relevant for evaluation of clinical trials and in designing future immunotherapeutic approaches of PC.


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