4.3 Article

Characterization of infiltrating lymphocytes in human benign and malignant prostate tissue

Journal

ONCOTARGET
Volume 8, Issue 36, Pages 60257-60269

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19528

Keywords

prostate cancer; benign prostatic hyperplasia; prostate-infiltrating lymphocytes; checkpoint blockade; PD-1

Funding

  1. Swedish Research Council
  2. Stockholm County Council
  3. Swedish Foundation of Strategic Research

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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 CCR7(-)CD45RO(+) 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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