Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Cytotoxic Activity and Memory T Cell Subset Distribution of in vitro-Stimulated CD8+ T Cells Specific for HER2/neu Epitopes. / Kuznetsova, Maria; Lopatnikova, Julia; Shevchenko, Julia и др.
в: Frontiers in Immunology, Том 10, № MAY, 1017, 09.05.2019, стр. 1017.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Cytotoxic Activity and Memory T Cell Subset Distribution of in vitro-Stimulated CD8+ T Cells Specific for HER2/neu Epitopes
AU - Kuznetsova, Maria
AU - Lopatnikova, Julia
AU - Shevchenko, Julia
AU - Silkov, Alexander
AU - Maksyutov, Amir
AU - Sennikov, Sergey
PY - 2019/5/9
Y1 - 2019/5/9
N2 - Minimal residual disease remaining after resection of primary tumors can lead to tumor recurrence and metastasis, increasing mortality and morbidity rates among cancer patients. Thus, there is a need for new technologies for recognition and elimination of single cancer cells remaining in a patient's body after radiation therapy, chemotherapy, or surgical resection. Effector CD8+ T cells, also commonly known as cytotoxic T lymphocytes (CTLs), play a key role in antitumor cellular immunity and, when properly activated, are able to effectively destroy tumor cells. The aims of this study were to obtain CD8+ CTLs specific for the HER2/neu epitopes E75 and E88 and to assess the cytotoxic activity and composition of these cells in terms of the distribution of memory T-cell subsets. We obtained HER2-specific CD8+ T cells and assessed T cell subset distribution among them including naive T cells (TN), central memory T cells (TCM), effector memory T cells (TEM), stem cell-like memory T cells (TSCM) and terminally-differentiated T cells (TEMRA) via eight-color flow cytometry. HER2-specific CTLs were largely (~40-50%) represented by TSCM cells, a population capable of mounting pronounced antitumor immune responses due to a combination of effector function and self-maintenance. In comparison with activated peripheral blood mononuclear cells (PBMCs) and bulk CD8+ T cells, HER2-specific CTLs exhibited greater cytotoxicity against the HER2-expressing human breast adenocarcinoma cell line MCF-7 and produced higher levels of IFN-γ in response to tumor cells. We also showed the presence of HER2-specific CTLs in healthy individuals and increase in them in HER2-positive breast cancer patients. Collectively, our results suggest that HER2-specific CD8+ T cells isolated using this approach could be used for adoptive T-cell transfer to eliminate tumor cells and prevent metastasis and relapse in patients with HER2-overexpressing cancers.
AB - Minimal residual disease remaining after resection of primary tumors can lead to tumor recurrence and metastasis, increasing mortality and morbidity rates among cancer patients. Thus, there is a need for new technologies for recognition and elimination of single cancer cells remaining in a patient's body after radiation therapy, chemotherapy, or surgical resection. Effector CD8+ T cells, also commonly known as cytotoxic T lymphocytes (CTLs), play a key role in antitumor cellular immunity and, when properly activated, are able to effectively destroy tumor cells. The aims of this study were to obtain CD8+ CTLs specific for the HER2/neu epitopes E75 and E88 and to assess the cytotoxic activity and composition of these cells in terms of the distribution of memory T-cell subsets. We obtained HER2-specific CD8+ T cells and assessed T cell subset distribution among them including naive T cells (TN), central memory T cells (TCM), effector memory T cells (TEM), stem cell-like memory T cells (TSCM) and terminally-differentiated T cells (TEMRA) via eight-color flow cytometry. HER2-specific CTLs were largely (~40-50%) represented by TSCM cells, a population capable of mounting pronounced antitumor immune responses due to a combination of effector function and self-maintenance. In comparison with activated peripheral blood mononuclear cells (PBMCs) and bulk CD8+ T cells, HER2-specific CTLs exhibited greater cytotoxicity against the HER2-expressing human breast adenocarcinoma cell line MCF-7 and produced higher levels of IFN-γ in response to tumor cells. We also showed the presence of HER2-specific CTLs in healthy individuals and increase in them in HER2-positive breast cancer patients. Collectively, our results suggest that HER2-specific CD8+ T cells isolated using this approach could be used for adoptive T-cell transfer to eliminate tumor cells and prevent metastasis and relapse in patients with HER2-overexpressing cancers.
KW - CD8+ T cells
KW - cytotoxicity
KW - HER2/neu
KW - memory T cell subsets
KW - stem cell-like memory T cells
KW - Memory T cell subsets
KW - Cytotoxicity
KW - Stem cell-like memory T cells
KW - IMMUNE-RESPONSE
KW - DENDRITIC CELLS
KW - CANCER
KW - BREAST
KW - IMMUNOTHERAPY
KW - BIOLOGY
KW - GROWTH
KW - CD8(+) T cells
KW - DIFFERENTIATION
KW - EXPRESSION
KW - LYMPHOCYTES
UR - http://www.scopus.com/inward/record.url?scp=85067296953&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2019.01017
DO - 10.3389/fimmu.2019.01017
M3 - Article
C2 - 31143180
AN - SCOPUS:85067296953
VL - 10
SP - 1017
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - MAY
M1 - 1017
ER -
ID: 20591660