Cargando…
Reduction of the CD16(−)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer
BACKGROUND: Natural cytotoxicity, mediated by natural killer (NK) cells plays an important role in the inhibition and elimination of malignant tumor cells. To investigate the immunoregulatory role of NK cells and their potential as diagnostic markers, NK cell activity (NKA) was analyzed in prostate...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817174/ https://www.ncbi.nlm.nih.gov/pubmed/24223759 http://dx.doi.org/10.1371/journal.pone.0078049 |
_version_ | 1782478030739865600 |
---|---|
author | Koo, Kyo Chul Shim, Doo Hee Yang, Chang Mo Lee, Saet-Byul Kim, Shi Mun Shin, Tae Young Kim, Kwang Hyun Yoon, Ho Geun Rha, Koon Ho Lee, Jae Myun Hong, Sung Joon |
author_facet | Koo, Kyo Chul Shim, Doo Hee Yang, Chang Mo Lee, Saet-Byul Kim, Shi Mun Shin, Tae Young Kim, Kwang Hyun Yoon, Ho Geun Rha, Koon Ho Lee, Jae Myun Hong, Sung Joon |
author_sort | Koo, Kyo Chul |
collection | PubMed |
description | BACKGROUND: Natural cytotoxicity, mediated by natural killer (NK) cells plays an important role in the inhibition and elimination of malignant tumor cells. To investigate the immunoregulatory role of NK cells and their potential as diagnostic markers, NK cell activity (NKA) was analyzed in prostate cancer (PCa) patients with particular focus on NK cell subset distribution. METHODS: Prospective data of NKA and NK cell subset distribution patterns were measured from 51 patients initially diagnosed with PCa and 54 healthy controls. NKA was represented by IFN-γ levels after stimulation of the peripheral blood with Promoca®. To determine the distribution of NK cell subsets, PBMCs were stained with fluorochrome-conjugated monoclonal antibodies. Then, CD16(+)CD56(dim) and CD16(−)CD56(bright) cells gated on CD56(+)CD3(−) cells were analyzed using a flow-cytometer. RESULTS: NKA and the proportion of CD56(bright) cells were significantly lower in PCa patients compared to controls (430.9 pg/ml vs. 975.2 pg/ml and 2.3% vs. 3.8%, respectively; p<0.001). Both tended to gradually decrease according to cancer stage progression (p for trend = 0.001). A significantly higher CD56(dim)-to-CD56(bright) cell ratio was observed in PCa patients (41.8 vs. 30.3; p<0.001) along with a gradual increase according to cancer stage progression (p for trend = 0.001), implying a significant reduction of CD56(bright) cells in relation to the alteration of CD56(dim) cells. The sensitivity and the specificity of NKA regarding PCa detection were 72% and 74%, respectively (best cut-off value at 530.9 pg/ml, AUC = 0.786). CONCLUSIONS: Reduction of CD56(bright) cells may precede NK cell dysfunction, leading to impaired cytotoxicity against PCa cells. These observations may explain one of the mechanisms behind NK cell dysfunction observed in PCa microenvironment and lend support to the development of future cancer immunotherapeutic strategies. |
format | Online Article Text |
id | pubmed-3817174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38171742013-11-09 Reduction of the CD16(−)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer Koo, Kyo Chul Shim, Doo Hee Yang, Chang Mo Lee, Saet-Byul Kim, Shi Mun Shin, Tae Young Kim, Kwang Hyun Yoon, Ho Geun Rha, Koon Ho Lee, Jae Myun Hong, Sung Joon PLoS One Research Article BACKGROUND: Natural cytotoxicity, mediated by natural killer (NK) cells plays an important role in the inhibition and elimination of malignant tumor cells. To investigate the immunoregulatory role of NK cells and their potential as diagnostic markers, NK cell activity (NKA) was analyzed in prostate cancer (PCa) patients with particular focus on NK cell subset distribution. METHODS: Prospective data of NKA and NK cell subset distribution patterns were measured from 51 patients initially diagnosed with PCa and 54 healthy controls. NKA was represented by IFN-γ levels after stimulation of the peripheral blood with Promoca®. To determine the distribution of NK cell subsets, PBMCs were stained with fluorochrome-conjugated monoclonal antibodies. Then, CD16(+)CD56(dim) and CD16(−)CD56(bright) cells gated on CD56(+)CD3(−) cells were analyzed using a flow-cytometer. RESULTS: NKA and the proportion of CD56(bright) cells were significantly lower in PCa patients compared to controls (430.9 pg/ml vs. 975.2 pg/ml and 2.3% vs. 3.8%, respectively; p<0.001). Both tended to gradually decrease according to cancer stage progression (p for trend = 0.001). A significantly higher CD56(dim)-to-CD56(bright) cell ratio was observed in PCa patients (41.8 vs. 30.3; p<0.001) along with a gradual increase according to cancer stage progression (p for trend = 0.001), implying a significant reduction of CD56(bright) cells in relation to the alteration of CD56(dim) cells. The sensitivity and the specificity of NKA regarding PCa detection were 72% and 74%, respectively (best cut-off value at 530.9 pg/ml, AUC = 0.786). CONCLUSIONS: Reduction of CD56(bright) cells may precede NK cell dysfunction, leading to impaired cytotoxicity against PCa cells. These observations may explain one of the mechanisms behind NK cell dysfunction observed in PCa microenvironment and lend support to the development of future cancer immunotherapeutic strategies. Public Library of Science 2013-11-04 /pmc/articles/PMC3817174/ /pubmed/24223759 http://dx.doi.org/10.1371/journal.pone.0078049 Text en © 2013 Koo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Koo, Kyo Chul Shim, Doo Hee Yang, Chang Mo Lee, Saet-Byul Kim, Shi Mun Shin, Tae Young Kim, Kwang Hyun Yoon, Ho Geun Rha, Koon Ho Lee, Jae Myun Hong, Sung Joon Reduction of the CD16(−)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer |
title | Reduction of the CD16(−)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer |
title_full | Reduction of the CD16(−)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer |
title_fullStr | Reduction of the CD16(−)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer |
title_full_unstemmed | Reduction of the CD16(−)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer |
title_short | Reduction of the CD16(−)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer |
title_sort | reduction of the cd16(−)cd56(bright) nk cell subset precedes nk cell dysfunction in prostate cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817174/ https://www.ncbi.nlm.nih.gov/pubmed/24223759 http://dx.doi.org/10.1371/journal.pone.0078049 |
work_keys_str_mv | AT kookyochul reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT shimdoohee reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT yangchangmo reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT leesaetbyul reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT kimshimun reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT shintaeyoung reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT kimkwanghyun reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT yoonhogeun reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT rhakoonho reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT leejaemyun reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer AT hongsungjoon reductionofthecd16cd56brightnkcellsubsetprecedesnkcelldysfunctioninprostatecancer |