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

2020 ◽  
Author(s):  
Yasmin Vahidi ◽  
Mandana Bagheri ◽  
Abbas Ghaderi ◽  
Zahra Faghih
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Axillary Lymph ◽  
Memory Cells ◽  
Color Flow ◽  
Draining Lymph Nodes

Abstract 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.

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

2020 ◽  
Author(s):  
Yasmin Vahidi ◽  
Mandana Bagheri ◽  
Abbas Ghaderi ◽  
Zahra Faghih
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Axillary Lymph ◽  
Memory Cells ◽  
Color Flow ◽  
Draining Lymph Nodes

Abstract 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 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 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 CD45low TCM was higher in tumor-involved nodes. Along with a decrease in the frequency of naive T cells, the higher frequency of CD45low 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 (CD45ROlow), 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.

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

2019 ◽  
Author(s):  
Yasmin Vahidi ◽  
Mandana Bagheri ◽  
Abbas Ghaderi ◽  
Zahra Faghih
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Axillary Lymph ◽  
Memory Cells ◽  
Color Flow ◽  
Draining Lymph Nodes

Abstract 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.

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

2019 ◽  
Author(s):  
Yasmin Vahidi ◽  
Mandana Bagheri ◽  
Abbas Ghaderi ◽  
Zahra Faghih
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Axillary Lymph ◽  
Memory Cells ◽  
Memory T Cell ◽  
Draining Lymph Nodes

Abstract 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 with four-color flow cytometry and analyzed with CellQuest Pro software.Results We observed that 47.65±2.66 of CD8+ lymphocytes expressed the CD45RO 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). Mean CD96 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO hi TCM and CD45RO low subsets, and TSCM was higher in patients with stage II compared to those with stage I disease (P<0.05). 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 T cell subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45 low TCM along with naive CD8 + lymphocytes was 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 (CD45RO low ) 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.

Memory CD4+ T cell subsets in tumor draining lymph nodes of breast cancer patients: A focus on T stem cell memory cells

2017 ◽  
Vol 41 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Yasmin Vahidi ◽  
Zahra Faghih ◽  
Abdol-Rasoul Talei ◽  
Mehrnoosh Doroudchi ◽  
Abbas Ghaderi
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
T Cell ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Memory Cells ◽  
Breast Cancer Patients ◽  
Draining Lymph Nodes

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

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yasmin Vahidi ◽  
Mandana Bagheri ◽  
Abbas Ghaderi ◽  
Zahra Faghih
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
Draining Lymph Nodes

scholarly journals Rapid Acquisition of Tissue-specific Homing Phenotypes by CD4+ T Cells Activated in Cutaneous or Mucosal Lymphoid Tissues

2002 ◽  
Vol 195 (1) ◽  
pp. 135-141 ◽  
Author(s):  
Daniel J. Campbell ◽  
Eugene C. Butcher
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Lamina Propria ◽  
Memory T Cells ◽  
Lymphoid Organs ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Intestinal Lamina Propria ◽  
Tissue Specific

Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of ‘tissue-specific’ adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattracant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4+ effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and α4β7, respectively. We show that within 2 d of systemic immunization CD4+ T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate α4β7, while those responding to antigen in intestinal lymph nodes selectively express high levels of α4β7 and acquire responsiveness to the intestinal chemokine thymus-expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.

scholarly journals Activated, Pro-Inflammatory Th1, Th17, and Memory CD4+ T Cells and B Cells Are Involved in Delayed-Type Hypersensitivity Arthritis (DTHA) Inflammation and Paw Swelling in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoyang Li ◽  
Shrikant Shantilal Kolan ◽  
Shuai Guo ◽  
Katarzyna Marciniak ◽  
Pratibha Kolan ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Delayed Type Hypersensitivity ◽  
Memory Cd4 T Cells ◽  
Draining Lymph Nodes

Delayed-type hypersensitivity arthritis (DTHA) is a recently established experimental model of rheumatoid arthritis (RA) in mice with pharmacological values. Despite an indispensable role of CD4+ T cells in inducing DTHA, a potential role for CD4+ T cell subsets is lacking. Here we have quantified CD4+ subsets during DTHA development and found that levels of activated, pro-inflammatory Th1, Th17, and memory CD4+ T cells in draining lymph nodes were increased with differential dynamic patterns after DTHA induction. Moreover, according to B-cell depletion experiments, it has been suggested that this cell type is not involved in DTHA. We show that DTHA is associated with increased levels of B cells in draining lymph nodes accompanied by increased levels of circulating IgG. Finally, using the anti-rheumatoid agents, methotrexate (MTX) and the anti-inflammatory drug dexamethasone (DEX), we show that MTX and DEX differentially suppressed DTHA-induced paw swelling and inflammation. The effects of MTX and DEX coincided with differential regulation of levels of Th1, Th17, and memory T cells as well as B cells. Our results implicate Th1, Th17, and memory T cells, together with activated B cells, to be involved and required for DTHA-induced paw swelling and inflammation.

scholarly journals In vivo photolabeling of tumor-infiltrating cells reveals highly regulated egress of T-cell subsets from tumors

2017 ◽  
Vol 114 (22) ◽  
pp. 5677-5682 ◽  
Author(s):  
Tommaso Torcellan ◽  
Henry R. Hampton ◽  
Jacqueline Bailey ◽  
Michio Tomura ◽  
Robert Brink ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Lymph Nodes ◽  
Immune Cells ◽  
Immune Therapy ◽  
T Cell Subsets ◽  
Primary Tumors ◽  
Infiltrating Cells ◽  
Draining Lymph Nodes

Immune therapy is rapidly gaining prominence in the clinic as a major weapon against cancer. Whereas much attention has been focused on the infiltration of tumors by immune cells, the subsequent fate of these infiltrates remains largely unexplored. We therefore established a photoconversion-based model that allowed us to label tumor-infiltrating immune cells and follow their migration. Using this system, we identified a population of tumor-experienced cells that emigrate from primary tumors to draining lymph nodes via afferent lymphatic vessels. Although the majority of tumor-infiltrating cells were myeloid, T cells made up the largest population of tumor-egressing leukocytes. Strikingly, the subset composition of tumor-egressing T cells was greatly skewed compared with those that had infiltrated the tumor and those resident in the draining lymph node. Some T-cell subsets such as CD8+ T cells emigrated more readily; others including CD4−CD8− T cells were preferentially retained, suggesting that specific mechanisms guide immune cell egress from tumors. Furthermore, tumor-egressing T cells were more activated and displayed enhanced effector function in comparison with their lymph node counterparts. Finally, we demonstrated that tumor-infiltrating T cells migrate to distant secondary tumors and draining lymph nodes, highlighting a mechanism whereby tumor-experienced effector T cells may mediate antitumor immunity at metastatic sites. Thus, our results provide insights into migration and function of tumor-infiltrating immune cells and the role of these cells in tumor immunity outside of primary tumor deposits.

scholarly journals Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications

2021 ◽  
Vol 12 ◽  
Author(s):  
Hannah-Lou Schilling ◽  
Gunther Glehr ◽  
Michael Kapinsky ◽  
Norbert Ahrens ◽  
Paloma Riquelme ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Color Flow ◽  
Skin Reactions

Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4+ effector memory T cells (TEM) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given αPD-1 and αCTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4+ TEM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4+ TEM cells (agreement = 98%) and is superior in resolving CD4+ CD197+ CD45RA- central memory T cells (TCM) from CD4+ CD197+ CD45RA+ naive T cells (Tnaive). It also enables us to precisely quantify CD14+ monocytes (CV = 6.6%). Our new “monocyte and T cell” (MoT) assay predicts immune-related hepatitis with a positive predictive value (PPV) of 83% and negative predictive value (NPV) of 80%. Our essential improvements open the possibility of sharing our predictive methods with other clinical centers. Furthermore, condensing measurements of monocyte and memory T cell subsets into a single assay simplifies our workflows and facilitates computational analyses.

scholarly journals High PD-1 expression on regulatory and effector T-cells in lung cancer draining lymph nodes

2017 ◽  
Vol 3 (2) ◽  
pp. 00110-2016 ◽  
Author(s):  
Rieneke van de Ven ◽  
Anna-Larissa N. Niemeijer ◽  
Anita G.M. Stam ◽  
Sayed M.S. Hashemi ◽  
Christian G. Slockers ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Endobronchial Ultrasound ◽  
Expression Levels ◽  
Number Of Patients ◽  
Draining Lymph Nodes

The treatment of advanced nonsmall cell lung cancer (NSCLC) with PD-1/PD-L1 immune checkpoint inhibitors has improved clinical outcome for a proportion of patients. The current challenge is to find better biomarkers than PD-L1 immunohistochemistry (IHC) that will identify patients likely to benefit from this therapy. In this exploratory study we assessed the differences in T-cell subsets and PD-1 expression levels on T-cells in tumour-draining lymph nodes (TDLNs) and peripheral blood mononuclear cells (PBMCs).To evaluate this, flow cytometric analyses were performed on endobronchial ultrasound-guided (EBUS) fine-needle aspirates (FNA) from TDLNs of patients with NSCLC, and the results were compared to paired PBMC samples. For a select number of patients, we were also able to obtain cells from a non-TDLN (NTDLN) sample.Our data show that the frequency of PD-1+ CD4+ and CD8+ T-cells, as well as the PD-1 expression level on activated regulatory T (aTreg) and CD4+ and CD8+ T-cells, are higher in TDLNs than in PBMCs and, in a small sub-analysis, NTDLNs.These elevated PD-1 expression levels in TDLNs may reflect tumour-specific T-cell priming and conditioning, and may serve as a predictive or early-response biomarker during PD-1 checkpoint blockade.

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