T-memory cells against cancer: Remembering the enemy

Sarkar, Irene; Pati, Subhadip; Dutta, Abhishek; Basak, Udit; Sa, Gaurisankar

doi:10.1016/j.cellimm.2019.03.002

Cited by 29 publications

(21 citation statements)

References 48 publications

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“…For T lymphocytes, long-lasting immune protection is achieved by the differentiation of naive T cells upon antigen stimulation into distinct memory cell lineages: central (TCM) and terminally committed effector memory T cells (TEM). These cells are characterized by selfrenewal capacity, clonal expansion, and faster attainment of effector functions upon antigen re-stimulation or challenge [2]. The repertoire of memory T cells was recently extended to diverse subtypes characterized by specific cell surface markers, unique homing properties, and special functional attributes [3].…”

Section: Introductionmentioning

confidence: 99%

“…T stem cells memory (TSCMs) were recently introduced as a rare subset of memory lymphocytes with the stem cell-like ability to self-renew and provide other memory and effector subsets [4][5][6]. Although these cells express naive markers they are more similar to memory subsets in function, as they express CD95 memory antigen and are antigen-experienced cells that respond rapidly to secrete effector cytokines [2]. These capabilities, along with recent evidence of their potential role in immune reconstitution in immunodeficient hosts and ability to mediate superior antitumor immunity in humanized mouse models, have brought TSCM cells to the attention of researchers in immunity and immunotherapies [7][8][9].…”

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.

show abstract

Section: Introductionmentioning

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

View full text Add to dashboard Cite

show abstract

“…For T lymphocytes, long-lasting immune protection is achieved by the differentiation of naive T cells upon antigen stimulation into 3 distinct memory cell lineages: central (TCM) and terminally committed effector memory T cells (TEM). These cells are characterized by self-renewal capacity, clonal expansion, and faster attainment of effector functions upon antigen re-stimulation or challenge [2]. The repertoire of memory T cells was recently extended to diverse subtypes characterized by specific cell surface markers, unique homing properties, and special functional attributes [3].…”

Section: Introductionmentioning

confidence: 99%

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

Vahidi¹,

Bagheri²,

Ghaderi³

et al. 2020

Preprint

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 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.

show abstract

“…Stem memory T cells (TSCMs) were recently introduced as a rare new subset of memory lymphocytes with the stem cell-like ability for self-renewal, and able to provide other memory and effector T cell subsets [4][5][6]. Although these cells express naive markers they are more similar to memory subsets in function, as they express CD95 memory antigen and are antigen-experienced cells that respond rapidly to secrete effector cytokines [2]. These capabilities, along with recent evidence of their potential role in immune reconstitution in immunodeficient hosts and ability to mediate superior antitumor immunity in humanized mouse models, have brought TSCM cells to the attention of researchers in immunity and immunotherapies [7][8][9].…”

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

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

T-memory cells against cancer: Remembering the enemy

Cited by 29 publications

References 48 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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