Relationship of Lymphocyte Subpopulations in Breast Cancer Patients With Treatment Results
Abstract: Introduction. Breast cancer (BC) is an immunogenic tumor. Immune cells infiltration of tumor tissue can affect the clinical course of the disease. The immunogenicity of breast cancer varies depending on the molecular subtype.The aim of this work was to study the main indicators of systemic and local immunity before patient’s treatment and to determine their relationship with the immediate neoadjuvant chemotherapy results.Materials and methods. Patients with stage II–III BC received standard neoadjuvant chemoth… Show more
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Features of the State of Cellular and Humoral Markers of the Immune System in Breast Cancer among Women in Aktobe Region
Abstract BACKGROUND: Globally, breast cancer is considered one of the most common cancers among women and the second most common cancer worldwide. Breast cancer is also more common in developed countries, and its prevalence is increasing globally by 2% each year. AIM: The aim of this study is to determine the features of the state of cellular and humoral markers of the immune system, as well as the relationship of specific and nonspecific immunity in women in the compared groups in breast cancer in Aktobe region. METHODS: The study was conducted on 251 patients at Medical Center of West Kazakhstan Marat Ospanov Medical University with the established diagnosis of breast cancer. The study period was 3 years (2018-2020). Acknowledgements. Authors declare the absence of conflict of interest. The study is funded by the Ministry of Education and Science of the Republic of Kazakhstan project IRN 0118RK01065. Two groups of patients were formed, among them in the control group - BC before chemotherapy and in the main group - BC after chemotherapy. To address the objectives, in addition to the general clinical study, all patients were conducted immune system study. CD3+CD19-, CD3-CD19+, CD4+CD8-,CD4-CD8+, IRI, CD3+HLA-DR+, NK(CD16+56+), CD3+/CD16+56+ ; and to determine humoral immunity, the content of JgM, JgG, JgA were determined. RESULTS: Correlation analysis revealed a strong positive relationship between IRI and T helper (CD4+CD8-) (r=0.79; p≤0.05) and a strong negative correlation between T cytotoxic lymphocyte (CD4-CD8+) and IRI (r= -0.8; p≤0.05) in both patient groups. The ratio of the two T cell subpopulations CD4+/T cell CD8+ is at the regulatory T cell level (IRI). A direct median correlation between T lymphocyte (CD3+CD19-) and T killer (CD3+/CD16+56+) r= 0.35; (p≤0.05) was found, which indicates an integral regulatory role of natural killer cells in immune system function. The following coorelation analysis showed a weak negative association between cellular and humoral immunity in the control group of women between T cytotoxic lymphocytes (CD4-CD8+) and IgG(r=-0.2; p≤0.05). Further, the relationship revealed between cellular and humoral immunity in the main group between IG M and NK cells (r= -0.2; p≤0.05). CONCLUSION: It can be assumed that identifying the possibility of altering the antitumor immune response before and after chemotherapy in patients with a primary breast tumor may set the stage for its early detection and application of targeted chemoprophylaxis. Abstract BACKGROUND: Globally, breast cancer is considered one of the most common cancers among women and the second most common cancer worldwide. Breast cancer is also more common in developed countries, and its prevalence is increasing globally by 2% each year. AIM: The aim of this study is to determine the features of the state of cellular and humoral markers of the immune system, as well as the relationship of specific and nonspecific immunity in women in the compared groups in breast cancer in Aktobe region. METHODS: The study was conducted on 251 patients at Medical Center of West Kazakhstan Marat Ospanov Medical University with the established diagnosis of breast cancer. The study period was 3 years (2018-2020). Acknowledgements. Authors declare the absence of conflict of interest. The study is funded by the Ministry of Education and Science of the Republic of Kazakhstan project IRN 0118RK01065. Two groups of patients were formed, among them in the control group - BC before chemotherapy and in the main group - BC after chemotherapy. To address the objectives, in addition to the general clinical study, all patients were conducted immune system study. CD3+CD19-, CD3-CD19+, CD4+CD8-,CD4-CD8+, IRI, CD3+HLA-DR+, NK(CD16+56+), CD3+/CD16+56+ ; and to determine humoral immunity, the content of JgM, JgG, JgA were determined. RESULTS: Correlation analysis revealed a strong positive relationship between IRI and T helper (CD4+CD8-) (r=0.79; p≤0.05) and a strong negative correlation between T cytotoxic lymphocyte (CD4-CD8+) and IRI (r= -0.8; p≤0.05) in both patient groups. The ratio of the two T cell subpopulations CD4+/T cell CD8+ is at the regulatory T cell level (IRI). A direct median correlation between T lymphocyte (CD3+CD19-) and T killer (CD3+/CD16+56+) r= 0.35; (p≤0.05) was found, which indicates an integral regulatory role of natural killer cells in immune system function. The following coorelation analysis showed a weak negative association between cellular and humoral immunity in the control group of women between T cytotoxic lymphocytes (CD4-CD8+) and IgG(r=-0.2; p≤0.05). Further, the relationship revealed between cellular and humoral immunity in the main group between IG M and NK cells (r= -0.2; p≤0.05). CONCLUSION: It can be assumed that identifying the possibility of altering the antitumor immune response before and after chemotherapy in patients with a primary breast tumor may set the stage for its early detection and application of targeted chemoprophylaxis. Abstract BACKGROUND: Globally, breast cancer is considered one of the most common cancers among women and the second most common cancer worldwide. Breast cancer is also more common in developed countries, and its prevalence is increasing globally by 2% each year. AIM: The aim of this study is to determine the features of the state of cellular and humoral markers of the immune system, as well as the relationship of specific and nonspecific immunity in women in the compared groups in breast cancer in Aktobe region. METHODS: The study was conducted on 251 patients at Medical Center of West Kazakhstan Marat Ospanov Medical University with the established diagnosis of breast cancer. The study period was 3 years (2018-2020). Acknowledgements. Authors declare the absence of conflict of interest. The study is funded by the Ministry of Education and Science of the Republic of Kazakhstan project IRN 0118RK01065. Two groups of patients were formed, among them in the control group - BC before chemotherapy and in the main group - BC after chemotherapy. To address the objectives, in addition to the general clinical study, all patients were conducted immune system study. CD3+CD19-, CD3-CD19+, CD4+CD8-,CD4-CD8+, IRI, CD3+HLA-DR+, NK(CD16+56+), CD3+/CD16+56+ ; and to determine humoral immunity, the content of JgM, JgG, JgA were determined. RESULTS: Correlation analysis revealed a strong positive relationship between IRI and T helper (CD4+CD8-) (r=0.79; p≤0.05) and a strong negative correlation between T cytotoxic lymphocyte (CD4-CD8+) and IRI (r= -0.8; p≤0.05) in both patient groups. The ratio of the two T cell subpopulations CD4+/T cell CD8+ is at the regulatory T cell level (IRI). A direct median correlation between T lymphocyte (CD3+CD19-) and T killer (CD3+/CD16+56+) r= 0.35; (p≤0.05) was found, which indicates an integral regulatory role of natural killer cells in immune system function. The following coorelation analysis showed a weak negative association between cellular and humoral immunity in the control group of women between T cytotoxic lymphocytes (CD4-CD8+) and IgG(r=-0.2; p≤0.05). Further, the relationship revealed between cellular and humoral immunity in the main group between IG M and NK cells (r= -0.2; p≤0.05). CONCLUSION: It can be assumed that identifying the possibility of altering the antitumor immune response before and after chemotherapy in patients with a primary breast tumor may set the stage for its early detection and application of targeted chemoprophylaxis.
Features of the State of Cellular and Humoral Markers of the Immune System in Breast Cancer among Women in Aktobe Region
Abstract BACKGROUND: Globally, breast cancer is considered one of the most common cancers among women and the second most common cancer worldwide. Breast cancer is also more common in developed countries, and its prevalence is increasing globally by 2% each year. AIM: The aim of this study is to determine the features of the state of cellular and humoral markers of the immune system, as well as the relationship of specific and nonspecific immunity in women in the compared groups in breast cancer in Aktobe region. METHODS: The study was conducted on 251 patients at Medical Center of West Kazakhstan Marat Ospanov Medical University with the established diagnosis of breast cancer. The study period was 3 years (2018-2020). Acknowledgements. Authors declare the absence of conflict of interest. The study is funded by the Ministry of Education and Science of the Republic of Kazakhstan project IRN 0118RK01065. Two groups of patients were formed, among them in the control group - BC before chemotherapy and in the main group - BC after chemotherapy. To address the objectives, in addition to the general clinical study, all patients were conducted immune system study. CD3+CD19-, CD3-CD19+, CD4+CD8-,CD4-CD8+, IRI, CD3+HLA-DR+, NK(CD16+56+), CD3+/CD16+56+ ; and to determine humoral immunity, the content of JgM, JgG, JgA were determined. RESULTS: Correlation analysis revealed a strong positive relationship between IRI and T helper (CD4+CD8-) (r=0.79; p≤0.05) and a strong negative correlation between T cytotoxic lymphocyte (CD4-CD8+) and IRI (r= -0.8; p≤0.05) in both patient groups. The ratio of the two T cell subpopulations CD4+/T cell CD8+ is at the regulatory T cell level (IRI). A direct median correlation between T lymphocyte (CD3+CD19-) and T killer (CD3+/CD16+56+) r= 0.35; (p≤0.05) was found, which indicates an integral regulatory role of natural killer cells in immune system function. The following coorelation analysis showed a weak negative association between cellular and humoral immunity in the control group of women between T cytotoxic lymphocytes (CD4-CD8+) and IgG(r=-0.2; p≤0.05). Further, the relationship revealed between cellular and humoral immunity in the main group between IG M and NK cells (r= -0.2; p≤0.05). CONCLUSION: It can be assumed that identifying the possibility of altering the antitumor immune response before and after chemotherapy in patients with a primary breast tumor may set the stage for its early detection and application of targeted chemoprophylaxis. Abstract BACKGROUND: Globally, breast cancer is considered one of the most common cancers among women and the second most common cancer worldwide. Breast cancer is also more common in developed countries, and its prevalence is increasing globally by 2% each year. AIM: The aim of this study is to determine the features of the state of cellular and humoral markers of the immune system, as well as the relationship of specific and nonspecific immunity in women in the compared groups in breast cancer in Aktobe region. METHODS: The study was conducted on 251 patients at Medical Center of West Kazakhstan Marat Ospanov Medical University with the established diagnosis of breast cancer. The study period was 3 years (2018-2020). Acknowledgements. Authors declare the absence of conflict of interest. The study is funded by the Ministry of Education and Science of the Republic of Kazakhstan project IRN 0118RK01065. Two groups of patients were formed, among them in the control group - BC before chemotherapy and in the main group - BC after chemotherapy. To address the objectives, in addition to the general clinical study, all patients were conducted immune system study. CD3+CD19-, CD3-CD19+, CD4+CD8-,CD4-CD8+, IRI, CD3+HLA-DR+, NK(CD16+56+), CD3+/CD16+56+ ; and to determine humoral immunity, the content of JgM, JgG, JgA were determined. RESULTS: Correlation analysis revealed a strong positive relationship between IRI and T helper (CD4+CD8-) (r=0.79; p≤0.05) and a strong negative correlation between T cytotoxic lymphocyte (CD4-CD8+) and IRI (r= -0.8; p≤0.05) in both patient groups. The ratio of the two T cell subpopulations CD4+/T cell CD8+ is at the regulatory T cell level (IRI). A direct median correlation between T lymphocyte (CD3+CD19-) and T killer (CD3+/CD16+56+) r= 0.35; (p≤0.05) was found, which indicates an integral regulatory role of natural killer cells in immune system function. The following coorelation analysis showed a weak negative association between cellular and humoral immunity in the control group of women between T cytotoxic lymphocytes (CD4-CD8+) and IgG(r=-0.2; p≤0.05). Further, the relationship revealed between cellular and humoral immunity in the main group between IG M and NK cells (r= -0.2; p≤0.05). CONCLUSION: It can be assumed that identifying the possibility of altering the antitumor immune response before and after chemotherapy in patients with a primary breast tumor may set the stage for its early detection and application of targeted chemoprophylaxis. Abstract BACKGROUND: Globally, breast cancer is considered one of the most common cancers among women and the second most common cancer worldwide. Breast cancer is also more common in developed countries, and its prevalence is increasing globally by 2% each year. AIM: The aim of this study is to determine the features of the state of cellular and humoral markers of the immune system, as well as the relationship of specific and nonspecific immunity in women in the compared groups in breast cancer in Aktobe region. METHODS: The study was conducted on 251 patients at Medical Center of West Kazakhstan Marat Ospanov Medical University with the established diagnosis of breast cancer. The study period was 3 years (2018-2020). Acknowledgements. Authors declare the absence of conflict of interest. The study is funded by the Ministry of Education and Science of the Republic of Kazakhstan project IRN 0118RK01065. Two groups of patients were formed, among them in the control group - BC before chemotherapy and in the main group - BC after chemotherapy. To address the objectives, in addition to the general clinical study, all patients were conducted immune system study. CD3+CD19-, CD3-CD19+, CD4+CD8-,CD4-CD8+, IRI, CD3+HLA-DR+, NK(CD16+56+), CD3+/CD16+56+ ; and to determine humoral immunity, the content of JgM, JgG, JgA were determined. RESULTS: Correlation analysis revealed a strong positive relationship between IRI and T helper (CD4+CD8-) (r=0.79; p≤0.05) and a strong negative correlation between T cytotoxic lymphocyte (CD4-CD8+) and IRI (r= -0.8; p≤0.05) in both patient groups. The ratio of the two T cell subpopulations CD4+/T cell CD8+ is at the regulatory T cell level (IRI). A direct median correlation between T lymphocyte (CD3+CD19-) and T killer (CD3+/CD16+56+) r= 0.35; (p≤0.05) was found, which indicates an integral regulatory role of natural killer cells in immune system function. The following coorelation analysis showed a weak negative association between cellular and humoral immunity in the control group of women between T cytotoxic lymphocytes (CD4-CD8+) and IgG(r=-0.2; p≤0.05). Further, the relationship revealed between cellular and humoral immunity in the main group between IG M and NK cells (r= -0.2; p≤0.05). CONCLUSION: It can be assumed that identifying the possibility of altering the antitumor immune response before and after chemotherapy in patients with a primary breast tumor may set the stage for its early detection and application of targeted chemoprophylaxis.
Backgraund. Currently, immunotherapy is firmly established in the standard of cancer treatment. The basis for the appointment of immunotherapy are immunological tumor markers, which include lymphoid infiltration, a detailed study of which has received increasing attention in the last decade. An undoubted interest is the study of lymphoid infiltration, not only depending on the morpho-clinical parameters of breast cancer (BC), but also on the immune system of the bone marrow.Aim. To evaluate the infiltration of the primary tumor by lymphocytes depending on the morpho-clinical characteristics of BC and immune responses in the bone marrow.Materials and methods. This study included 125 patients with BC who received treatment at the “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia. Tumor stage II was prevailed, а moderate degree of differentiation (G2) was more often noted. The luminal BC – 67 %, non-luminal – 33 %. Immunophenotyping of the primary tumor: cryostat sections, ZEISS Axioscope luminescent microscope (Zeiss AG, Germany). CD45+, CD38+, T- and B-cell infiltration were assessed. Bone marrow: CD3+, CD4+, CD8+, CD19+, CD16+, CD56+ lymphocytes and their subpopulations were studied (FACSCanto II flow cytometer, Kaluza Analysis v2.1 program (Beckman Coulter, USA)).Results. CD45+ infiltration was noted in 50.5 % of cases (severe in 30 %, moderate – 26.4 %). CD8+ cells significantly infiltrated the tumor in 21.4 % of cases. CD38+ infiltration was observed in 40 %. In the non-luminal BC, severe CD45 infiltration was observed more frequently than in the luminal (33 % vs 26 %). CD38+ infiltration is expressed in non-luminal BC (p = 0.016). CD45+ infiltration was positively correlated with earlier stages (p = 0.071) more pronounced in infiltrative ductal BC, than in lobular BC: 59.2 % vs 20 % (p = 0.05). The content of CD45RO+cells in bone marrow in the luminal BC is higher than in the non-luminal: 37.3 ± 2.3 % vs 28 ± 2.8 % (p = 0.04). The number of CD19+CD38+ cells, on the contrary, is less: 24.2 ± 2 % vs 34.8 ± 6 % (p = 0.041). Tumor-infiltrating lymphocytes highly correlated with bone marrow lymphoid populations: CD38+ cells with NK-bone marrow cells; CD4+ cells with the B-precursors; CD8+cells with the B1-lymphocytes.Conclusion. Lymphoid infiltration of BC is associated with stage, tumor size, histological type and biological subtype. Intratumoral populations CD38+, CD4+, CD3+, CD8+ cells are in a negative correlation with bone marrow lymphoid populations.
Subpopulation structure of tumor-infiltrating lymphocytes in early and locally advanced triple negative breast cancer and its effect on the efficiency of neoadjuvant chemotherapy
Recent studies have shown that triple-negative breast cancer (TN BC) is characterized by the highest mutational load and immunogenicity compared to other subtypes, as well as the degree of tumor-infiltrating lymphocytes (TILs) infiltration, which play an important role in the development of antitumor immunity and treatment response. A significant disadvantage of the standard immunohistochemical method for determining TILs is the inability to fully assess the subpopulation structure of the immune infiltration, including minor populations.Aim: The evaluation of the subpopulations of breast cancer lymphoid infiltration in patients receiving neoadjuvant chemotherapy (NACT) and its influence on achieving a complete pathomorphological response (pCR = RCB 0).Materials and methods: The study included 90 patients who received NACT in following regimen: AC (doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 ) every 2 weeks, followed by 12 weekly infusions of paclitaxel 80 mg/m2 + carboplatin AUC2. The TILs subpopulations were evaluated in core-biopsy samples prior to the NACT in all patients. The analysis performed by flow cytofluorimetry. Clinical and immunological analysis was performed for the following 9 lymphocyte subpopulations: CD3+CD4+, CD3+CD8+, CD4+CD25highCD127– / low, CD3–CD19+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+, CD8+CD279+, CD4+CD279+.Results: The frequency of pCR was 51,1 %. The total TILs content in groups with pCR and non-pCR (RCB 0 vs RCB I–III) did not differ statistically (p = 0.271). The subpopulations analysis for CD3+CD8+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD3+CD4+, CD3–CD19+, CD4+CD25+, CD4+CD25highCD127– / low and CD4+CD279+ revealed no statistically significant differences between the median values in the groups with pCR and non-pCR. A study of the CD8+CD279+ population showed a higher level of these cells in patients achieved pCR / RCB 0 (median 18,6 % vs 12,3 % with RCB I–III) (p = 0.033). With CD8+CD279+ above the median (high, > Me), the pCR frequency was 61 % vs 35 % in the subgroup with CD8+CD279+ less than or equal to the median (low, ≤Me). Despite the absence of statistically significant differences in the content of CD3+CD16+CD56+(NKT-cells) in groups with pCR and non-pCR (p = 0.091), numerical differences in medians were revealed: 9,9 % and 8,3 %, respectively. At the same time, with CD3+CD16+CD56+(NKT) > Me (high), the pCR frequency was 63 % vs 36 % in the subgroup with CD3+CD16+CD56 + ≤Me (low). When selecting a narrow subgroup (CD8+CD279+ high and CD3+CD16+CD56+ high), the frequency of pCR was 87,5 % vs 27,3 % in the group with both low indicators.Conclusion: The high content of CD8+CD279+ and CD3+CD16+CD56+ in the tumor sample before the treatment start was a predictor of high sensitivity to NACT and is associated with a higher frequency of pCR.
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