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CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer

BACKGROUND: Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8(+) memory T cell subsets including T stem cell memory (TS...

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Autores principales: Vahidi, Yasmin, Bagheri, Mandana, Ghaderi, Abbas, Faghih, Zahra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106627/
https://www.ncbi.nlm.nih.gov/pubmed/32228503
http://dx.doi.org/10.1186/s12885-020-6714-x
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author Vahidi, Yasmin
Bagheri, Mandana
Ghaderi, Abbas
Faghih, Zahra
author_facet Vahidi, Yasmin
Bagheri, Mandana
Ghaderi, Abbas
Faghih, Zahra
author_sort Vahidi, Yasmin
collection PubMed
description BACKGROUND: Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8(+) memory T cell subsets including T stem cell memory (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC). METHODS: Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8(+) lymphocyte population. Data were acquired on four-color flow cytometer and analyzed with CellQuest Pro software. RESULTS: We observed that 47.65 ± 2.66% of CD8(+) lymphocytes expressed the CD45RO, a marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P = 0.024 and P = 0.017, respectively). The level of CD95 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO(hi) and CD45RO(low) subsets, and TSCM was higher in patients with stage II compared to those in stage I (P < 0.05). In addition, the percentage of naive CD8(+) T cells was significantly lower in tumor-involved lymph nodes compared to tumor-free ones (P = 0.025). CONCLUSIONS: Our data collectively indicate no significant differences in the frequencies of CD8(+) lymphocytes or their memory subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45(low) TCM was higher in tumor-involved nodes. Along with a decrease in the frequency of naive T cells, the higher frequency of CD45(low) TCM suggests that despite the immune reaction to provide a pool of effective memory cells, it is blocked in early-stage of memory cells’ differentiation (CD45RO(low)), probably by tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.
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spelling pubmed-71066272020-04-01 CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer Vahidi, Yasmin Bagheri, Mandana Ghaderi, Abbas Faghih, Zahra BMC Cancer Research Article BACKGROUND: Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8(+) memory T cell subsets including T stem cell memory (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC). METHODS: Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8(+) lymphocyte population. Data were acquired on four-color flow cytometer and analyzed with CellQuest Pro software. RESULTS: We observed that 47.65 ± 2.66% of CD8(+) lymphocytes expressed the CD45RO, a marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P = 0.024 and P = 0.017, respectively). The level of CD95 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO(hi) and CD45RO(low) subsets, and TSCM was higher in patients with stage II compared to those in stage I (P < 0.05). In addition, the percentage of naive CD8(+) T cells was significantly lower in tumor-involved lymph nodes compared to tumor-free ones (P = 0.025). CONCLUSIONS: Our data collectively indicate no significant differences in the frequencies of CD8(+) lymphocytes or their memory subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45(low) TCM was higher in tumor-involved nodes. Along with a decrease in the frequency of naive T cells, the higher frequency of CD45(low) TCM suggests that despite the immune reaction to provide a pool of effective memory cells, it is blocked in early-stage of memory cells’ differentiation (CD45RO(low)), probably by tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer. BioMed Central 2020-03-30 /pmc/articles/PMC7106627/ /pubmed/32228503 http://dx.doi.org/10.1186/s12885-020-6714-x Text en © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Vahidi, Yasmin
Bagheri, Mandana
Ghaderi, Abbas
Faghih, Zahra
CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer
title CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer
title_full CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer
title_fullStr CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer
title_full_unstemmed CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer
title_short CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer
title_sort cd8-positive memory t cells in tumor-draining lymph nodes of patients with breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106627/
https://www.ncbi.nlm.nih.gov/pubmed/32228503
http://dx.doi.org/10.1186/s12885-020-6714-x
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