Importance of CD45RO+ tumor-infiltrating lymphocytes in post-operative survival of breast cancer patients

Ahmadvand, Simin; Faghih, Zahra; Montazer, Mehdi; Safaei, Akbar; Mokhtari, Maral; Jafari, Peyman; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Ghaderi, Abbas

doi:10.1007/s13402-019-00430-6

Cited by 29 publications

(35 citation statements)

References 49 publications

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“…There is a general consensus that in the context of the antitumor immune response, the frequency of CD8 + lymphocytes and their memory T cell subsets correlates positively with smaller tumor size, lower disease stages, less lymph node involvement, and a generally better prognosis or survival in most types of cancer, e.g. breast carcinoma [14,[16][17][18][19][20][21][22]. CD8 + lymphocytes are assumed to mediate tumor rejection through the direct killing of transformed cells.…”

Section: Discussionmentioning

confidence: 99%

“…However, the suppressive tumor microenvironment often impairs their functionality through a set of transcriptional, functional, and phenotypic changes [10,12]. Thus the present study, to extend our previous work on memory cells in tumors [13,14], was designed to investigate the role of CD8 + lymphocytes and their memory cell subsets in tumor-draining lymph nodes (TDLNs) of patients with breast cancer (BC), and to identify their associations with clinical and pathological features.…”

Section: Introductionmentioning

confidence: 99%

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

Vahidi

Bagheri²,

Ghaderi

et al. 2020

BMC Cancer

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Vahidi

Bagheri²,

Ghaderi

et al. 2020

BMC Cancer

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show abstract

Section: Discussionmentioning

confidence: 99%

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

Vahidi¹,

Bagheri²,

Ghaderi³

et al. 2020

Preprint

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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 stem memory T cells (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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“…Thus the present study, to extend our previous work on memory cells in tumors [13,14], was designed to investigate the role of CD8 + lymphocytes and their memory cell subsets in tumordraining lymph nodes (TDLNs) of patients with breast cancer (BC), and to identify their associations with clinical and pathological features.…”

Section: Introductionmentioning

confidence: 99%

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

Vahidi¹,

Bagheri²,

Ghaderi³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

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 stem memory T cells (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 cytometry 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 CD45ROhi and CD45ROlow 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 higher 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 frequencies of CD45low TCM along with naive CD8+ lymphocytes were higher in tumor-involved nodes, which suggests that after long-term exposure to the antigen, and despite the immune reaction in order to provide a pool of effective memory cells, memory cell differentiation is blocked in early-stage (CD45ROlow) due to tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.

show abstract

Importance of CD45RO+ tumor-infiltrating lymphocytes in post-operative survival of breast cancer patients

Cited by 29 publications

References 49 publications

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

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

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

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

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