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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.
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.
According to world Health Organization, breast cancer (BC) ranks first among cancer diseases in women in many developed countries of the world and in the Russian Federation. Over the past 20 years, the incidence of breast cancer in the world has increased and continues to increase. This phenomenon dictates the need for a more in-depth molecular biological, genetic and immunological study of the mechanisms of development and progression of this heterogeneous malignant tumor.Recently, there has been increasing interest in the world not on lyin the direct causes of tumor development, but also in factors contributing to its progression, such as the cellular microenvironment of the tumor, the composition of which has a great influence on cancer development, treatment and prognosis. In the cellular microenvironment of the tumor, mononuclear cells are assessed, the proportion of which determines the severity and direction of the immuneresponse. Their importance for choosing the priority type of drug therapy and assessing its effectiveness is shown. The article provide scurrent data on subpopulations of T cells (CD8+, CD4+), B cells (CD20+), and natural killer. Their role in the development and progression of breast cancer is discussed depending on their phenotype. Modern research pays attention to a minor subpopulation of T lymphocytes – TCR-Vδ1+ cells. This subpopulation is represented predominantly in tumor tissue and has an immunosuppressive effect on T-effectors. At the present stage, inflammatory cells – macrophages and neutrophils – are of no less interest. Their role in tumor progression is widely debated. It is known that the differentiation of macrophages into M1 or M2 phenotypes is determined by the tumor microenvironment. The predominance of macrophages with protumor activity promotes tumor progression and cancer metastasis. Additionally, macrophages can stimulate the migration of neutrophils, which, in turn, support the metastasis of breast cancer through the production of matrix metalloproteinases. Matrix metalloproteinase 9 has been reported to promote the formation of vascular endothelial growth factor, which explains the protumor properties of neutrophils. In the context of growing tumor immunotherapy, assessment of tumor microenvironmental factors is promising both in relation to monitoring the effectiveness of breast cancer therapy and in relation to the search for potential therapeutic targets. The review systematizes and summarizes information on this issue to date.
Introduction. An important aspect of cancer treatment today is the concept of immuno-targeted therapy, which requires a deep understanding of the characteristics of immune reactions in the body of a cancer patient. Bone marrow is the central organ of immunopoiesis, therefore, along with the study of tumor characteristics, attention is paid to the bone marrow. The study of the cellular composition of the bone marrow in some types of cancer revealed a number of features of hematopoiesis, which requires further deeper analysis.Purpose. To study the parameters of hematopoiesis in patients with primary and recurrent ovarian cancer.Materials and methods. The paper presents data from 68 patients with a verified diagnosis of primary (n = 43) and recurrent (n = 25) ovarian cancer. The study was dominated by serous adenocarcinoma of high grade. Stage I was established in 13.2 % of cases, II – in 5.9 %, III – in 60.3 %, IV – in 20.6 %. The bone marrow was harvested by puncture of the posterior iliac spine (spina iliaca posterior superior). Parameter assessment and myelogram calculation were performed by two physicians, morphologists. The content of myelokaryocytes, indicators of granulocyte, erythroid lineage, the content of lymphocytes, monocytes were analyzed, and myelogram indices were assessed. In all patients microscopy of bone marrow samples excluded metastatic lesions. Statistical data processing was performed using the SPSS Statistics v. 21 package.Results. The analysis of bone marrow samples from patients with ovarian cancer revealed differences with the norm for both primary and recurrent ovarian cancer. Most punctates were normocellular, but average myelokaryocyte count in both groups was below normal. With recurrent ovarian cancer, a reduced content of promyelocytes and metamyelocytes was noted, whereas with primary cancer, all young forms of neutrophils was below normal. An increase in segmented neutrophils without a change in the percentage of cells of the granulocytic lineage was observed in primary ovarian cancer, and in one third of the samples of bone marrow an increased number lymphocytes and monocytes were noted. With recurrent ovarian cancer lymphocytes were increased in 2/3 of samples, monocyte – in 48 %. A change in the proportion of cells of the erythroid lineage was observed in both recurrent and primary cancers: depletion of the pool of basophilic normoblasts and polychromatophils with an unchanged number of erythrokaryocytes, an increase in oxyphilic forms were noted.Conclusion. The revealed changes in hematopoiesis in ovarian cancer reflect the aggressive course of high-grade tumors, which can be considered as a result of the systemic influence of the tumor, and the obtained data can serve as the basis for a detailed immunophenotypic study of bone marrow in ovarian cancer.
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