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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15613-e15613
    Abstract: e15613 Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer. More than 60% of all cases of CRC are colon cancer (CC). The role of individual units of the immune system in the development of this tumor is ambiguous. The purpose of this study was to characterize local populations and subpopulations of immunocompetent cells in colorectal cancer with different tumor locations. Methods: The study included 50 CC (adenocarcinoma) patients aged 35-86 years, women n = 26 (52%). Stage I tumors were registered in 4 patients (8%), stage II 25 (50%), stage III 21 (42%). 20 patients (40%) had right-sided CC (group 1), 9 (18%) left-sided CC (group 2), and 21 (42%) sigmoid CC (group 3). All patients received surgical treatment. Cell suspensions were obtained from tumor (TT) and peritumoral tissues (PT) (1-3 cm from the tumor), and then processed with an antibody panel in accordance with the manufacturer instructions (Becton Dickinson, USA) to identify the main populations and subpopulations of leukocytes and lymphocytes. The relative number of major populations and subpopulations of lymphocytes was determined on the BD FACSCanto flow cytometer. Results: A decrease in lymphocytic infiltration was noted left-sided tumors and sigmoid tumors compared to right-sided CC, by 46% and 51%, respectively. The percentage of CD3+ cells was almost the same regardless of the colon tumor location, and the number of main populations of T lymphocytes differed: in group 3, the content of CD4+ cells was 21% higher, and CD8+ cells were 22% lower compared with group 1, while group 2 had no differences. Group 2 differed in the tumor infiltration with both NK and NKT lymphocytes, which were higher by 25% and 22%, respectively, than in group 1. An increase in NK cells was noted in the sigmoid colon (group 3), and the relative number of NKT lymphocytes decreased. A common feature of TT in groups 2 and 3 was an increase in the content of B lymphocytes by 98% and 133%, respectively. PT of group 2 showed a decrease by 72%, 33%, 66%, and 46% in the relative number of lymphocytes, CD4+, NKT and B lymphocytes compared with group 1, together with an increased content of NK and CD8+ lymphocytes. PT in patients of group 3 had a decrease in the number of total and NK lymphocytes by 46% and 26%, respectively, and a significant increase by 85% in the content of CD8+ cells, with no changes in CD3+, CD4+ cells, B and NKT lymphocytes. Conclusions: The local immune status of CRC patients demonstrated a number of differences: right-sided tumors were characterized by a higher T-lymphocytic infiltration with the same tendency in the perifocal tissues, while left-sided and sigmoid tumors showed higher B-lymphocytic infiltration, which can help in the disease prognosis and choice of treatment strategy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e12589-e12589
    Abstract: e12589 Background: Breast reconstruction after mastectomy for breast cancer (BC) is an important rehabilitation stage. Breast prosthesis implantation is sometimes accompanied by different complications which can be influenced by the immune system status. The aim of this study was to identify characteristics of the local cytokine profile in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Levels of cytokines IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, and TNF-α were determined by ELISA in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery. Results: Levels of IL-6 in wound fluid of patients with TI statistically significantly decreased by 43% (p=0.036) and 41% (p=0.039) on days 3-4 and 7 after the surgery, and IL-2 decreased by 27% (p=0.045) with its further increase by 44% (p=0.037) compared to day 1. A pronounced increase of the IFN-γ levels by 118% (p=0.018) and 158% (p=0.012) was registered respectively on days 3-4 and 7 after surgery. Conclusions: Reconstructive surgery with TI is followed by a local increase in levels of IL-2 and IFN-γ which may indicate increasing antitumor potential of the microenvironment. The revealed decrease in IL-6 levels after TI implantation indicates certain features of the inflammatory reaction development in the intervention site.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e15597-e15597
    Abstract: e15597 Background: Oncolytic virotherapy is developing intensively in modern oncology. Viruses demonstrate the ability to the direct oncolysis and to the stimulation of antitumor immune activity; this experiment was aimed at solving the question of the prevalence of one of them. Glial tumors are the most common brain tumors; oncolytic viruses show certain prospects in their treatment due to the ability to penetrate the blood-brain barrier. The aim of the study was to determine the possible oncolytic effect of new unclassified group K rotaviruses (RVK) on T98G and U87MG glioblastoma cells in vitro. Methods: T98G and U87MG cell cultures were received from Russian banks of cell lines of human and animal tissues. Standard culturing was performed with attenuated apatogenic RVK strains No. 100 and No. 228 at a concentration of 10 8 , 10 7 , 10 6 and 10 5 particles/mL. The cytotoxic effect was determined with MTT and Annexin V assays, cell morphology was evaluated by the light-optical method. Results: Both RVK strains demonstrated a dose-dependent cytotoxic activity; the maximal effect was observed in strain No.100 at a dose of 10 8 particles/mL on U87MG cells (predominantly apoptosis). Studies of cell morphology showed a pronounced effect of RVK on the cell culture: significant degenerative changes in cells, a tendency to a decrease in cluster size, a change in their shape and granularity. Cluster formation in culturing in the serum-free medium is considered in the literature as a property of cancer stem cells responsible in vivo for tumor recurrence and its chemo- and radio-resistance. T98G cells demonstrated morphological changes: nuclear segmentation, diffused cytoplasm, indistinct cell borders with signs of syncytium formation. Conclusions: The established oncolytic effect of RVK strain No. 100 in vitro on glioma cells, presumably with tumor stem cells, indicates a significant potential for the use of these rotaviruses in treatment of glial tumors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e13089-e13089
    Abstract: e13089 Background: Cancer stem cells (CSC) are a population in the complex hierarchy of tumor tissue responsible for growth, metastasis and resistance to chemotherapy and radiotherapy. The purpose of the study was to reveal the effect of the enzymatic disintegration of breast cancer (BC) tissue on the CSC immunophenotype. Methods: BC tumor samples obtained during surgery were placed for 2 hours in a sterile Hanks’ solution immediately after collection. Samples were fragmented to 1 mm in diameter, the fragments were evenly distributed into 4 Petri dishes with (6 cm diameter) and placed in DMEM medium (Gibco, USA) without collagenase and with the addition of collagenase (Biolot, Russia) to a final concentration of 150, 300 and 450 units/ml. Samples were cultured for 48 hours at 37°C and 5.5% CO 2 . On day 2, the samples incubated in collagenase were grinded by passing through tips of decreasing diameter; the reference sample was grinded in the Medimachine system (BD, USA). The effect of enzymatic tissue disintegration on the preservation of BC SC immunophenotype (CD24 low/- CD44 + ) was evaluated using the BD FacsCanto II flow cytometer (BD, USA) and PE Mouse Anti-Human CD24 (clone ML5; BD, USA) and FITC Mouse Anti-Human CD44 (clone G44-26; BD, USA) antibodies. Results: The total number of isolated cells increased almost exponentially with increasing collagenase concentration. The trypan blue test showed that cell viability did not change significantly with an increase in collagenase concentration and was approximately 50%, being an order of magnitude higher compared to mechanical dissociation (4%). However, 48 h incubation in a collagenase solution led decreased the number of CD44+ cells in proportion to the enzyme concentration by 3 to 10 times in comparison with the control. Similarly, inhibition of CD24 expression was observed compared with the control, inevitably leading to a decreased purity of the isolated subpopulation with the CD24 low/- CD44 + phenotype. Conclusions: Despite an increase in the yield of viable cells, prolonged incubation in a collagenase solution leads to a loss of the immunophenotype of BC SC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15503-e15503
    Abstract: e15503 Background: The purpose of this study was to analyze the effect of the CD44+ and CD133+ co-expression in cancer stem cells (CSCs) on lymphocytic microenvironment of colon cancer (CC). Methods: 200 CC patients received surgery as the first stage of treatment. The percentage of CSCs with the expression of CD44+ and/or CD133+ markers was studied in the tumor homogenates by flow cytometry, as well as some indicators of local immunity (CD3+, CD4+, CD8+, T regs (CD4+CD25+CD127dim), CD19+, PD-1, PD-L1, Th0, Tm, CD16/56+ and immunophenotypic characteristics of tumor cells (PD-L1, MHC-ABC). Results: Gradation depending on the absence or presence of co-expression of CSC markers on tumor cells allowed identification of 11 statistically significant differences out of 17 studied parameters of tumor cells and their lymphocytic microenvironment. Co-expression of CSC markers was accompanied by higher percentage of T regs (7.3±0.4 versus 5.3±0.5%), together with lower levels of CD4+ cells. At the same time, a higher content of the total number of T-lymphocytes was noted due to CD8+ with an increase in the percentage of memory T cells and a decline in naive T lymphocytes within this subpopulation. In addition, the co-expression of CSC markers was accompanied by a lower content of PD-L1 (34.3±3.0 vs. 42.9±2.5%) on lymphocytes and its higher content on tumor cells (10.6±1.5 vs. 4.1±0.8%), while the PD-1 expression on lymphocytes was higher (38.4±3.7 versus 22.3±2.9%). The presence of CD44+CD133+ CSCs was also accompanied by lower percentage of tumor cells expressing MHC class I (60.4±4.9 vs. 79.3±7.6%), which characterized the inhibition of recognition processes, and increased levels of CD8+, perhaps, should be considered as compensatory. Conclusions: The lymphocytic microenvironment of CC in the presence of CSCs with the CD44+CD133+ immunophenotype seems to be more immunosuppressive, according to the increase in the local content of T regs and the decrease in MHC-ABC expression. Higher expression of PD-L1 on tumor cells and PD-1 on lymphocytes allows activation of the PD-1/PD-L1 interaction, which enhances the immunosuppressive and growth-stimulating properties of the tumor microenvironment, but at the same time, makes tumor cells adequate targets for immunotherapy with immune checkpoint inhibitors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e12588-e12588
    Abstract: e12588 Background: Breast reconstruction after skin-sparing mastectomy for breast cancer (BC) is an important rehabilitation stage. Its results depend on many factors, with the immune system status playing the main role. The purpose of this study was to identify characteristics of the local lymphocyte populations in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Populations and subpopulations of lymphocytes were determined in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery using the FacsCanto II flow cytometer (Becton Dickinson, USA) with markers: CD3 FITC /CD15+56 PE /CD45 PerCP /CD4 PE-Cy7/CD19 APC/ CD8 APC-Cy7; CD45RA FITC /CD45RO PE /CD3 PerCP /CD8 APC; CD45RA FITC /CD62L PE /CD3 PerCP /CD4 APC; CD4 FITC /CD127 PE /CD3 PerCP / CD25 APC-Cy7; CD4 FITC /CD38PE /CD3 PerCP / HLADR APC. At least 50,000 cells were accumulated in each sample for the analysis. Results: The relative number of total lymphocytes exceeded the initial values by 3.3 (p=0.025) and 10.9 (p=0.012) times, respectively, on days 3-4 and 7 after surgery. Levels of CD3+CD4+ cells increased gradually and were 29% (p=0.042) higher by day 7, while levels of CD3+CD8+ decreased during the whole observation period. Levels of Tregs did not change, while B lymphocytes decreased by 36% (p=0.035) and 67% (p=0.026), respectively, on days 3-4 and 7. The levels of activated T lymphocytes increased by 33% (p=0.038) on days 3-4, compared with the initial values, probably due to the elevation of CD3+CD8+ levels (by 32%, p=0.037). The number of activated T lymphocytes with the CD3+CD4+ phenotype increased by 44% (p=0.024) on days 6-7. While the content of CD3+CD4+ cells with early activation markers (CD38+) significantly decreased (by 40%, p=0.031) and remained the same on days 3-4 and 7, the number of CD3+CD8+ with similar markers (CD38+) significantly increased by 28% (p=0.044) and 43%. Conclusions: TI implantation was accompanied by the activation of the cytotoxic T unit during the observation period, together with a decrease in immunosuppressive populations of lymphocytes, which may indicate a favorable development of the patient's body reaction.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e14539-e14539
    Abstract: e14539 Background: Promising oncolytic viruses are evaluated, as a rule, by their direct cytotoxic effect on cancer cells. However, the positive effect of cancer virotherapy may be associated with an effect on the immune system, in particular, on the expression of PD-1 and PD-L1 on lymphocytes. The aim of the study was to evaluate the effect of unclassified non-pathogenic strains of rotaviruses RVK100 and RVK228 on the expression of PD-1 and PD-L1 on peripheral blood T-cells of breast cancer patients. Methods: PBMC were cultured at 10 6 cells/ml cell density in RPMI 1640 medium (Gibco, USA) without the addition of serum at 37°C in an atmosphere containing 5.0% CO 2 . Four experimental variants were established - 1) negative control without the addition of viruses, 2) positive control of activation with phytohemagglutinin (PHA) addition, 3) addition of RVK100 strain in concentration 10 7 particles/ml, 4) addition of RVK228 strain in concentration 10 7 particles/ml. After 24 and 72 hours of incubation, the expression of PD-1 (CD279) and PD-L1 (CD274) on T cells was determined by flow cytometry. Results: After 24 hours of cultivation, an increase in PD-1 expression on CD4+ cells was observed in samples with addition of PHA - 40.5%, RVK100 - 42.3% and RVK228 - 37.5% compared with the control (18.1%). A similar, although less pronounced increase in PD-1 expression, was observed on CD8+ cells: PHA - 41.7%, RVK100 - 46.4%, RVK228 - 42.6% compared with 27.7% in the control. Expression of PD-L1 on CD4+ cells increased to 67.0% and 58.6% in samples with addition of RVK100 and RVK228 strains, respectively, while under the influence of PHA it increased to 75.1% compared with the control (44.8%). A similar trend was also found on CD8+ cells (control - 46.2%, RVK100 - 63.4%, RVK228 - 58.4%, PHA - 52.8%). After 72 hours, an increase in PD-1 expression on CD4+ cells was observed only in the control (up to 41.2%), while in the experimental variant with RVK100 addition there was a 2-fold decrease (up to 21.6%) and no significant changes were found in samples with addition of PHA and RVK228 compared to 24 h. At the same time, cultivation with RVK100 caused a decrease in PD-1 expression on CD8+ cells by 2.7 times (up to 17.4%) compared with 24 h, without significant changes in other samples (control - 33.1%, PHA - 48.1%, RVK228 - 38.4%). The expression of PD-L1 on CD4+ cells generally remained unchanged compared to 24 h, while proportion of CD8+CD279+ cells increased in all variants and reached 67-79% the in experimental and control samples. Conclusions: Both strains, like the nonspecific T-mitogen PHA, stimulated the expression of immune checkpoint receptors PD-1 and PD-L1 on T-helpers and CTLs after 24 hours of cultivation. After 72 hours of cultivation, RVK100, in contrast to RVK228, was able to reduce the expression of PD-1 on these cells.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15502-e15502
    Abstract: e15502 Background: The purpose of this study was a comparative analysis of the expression of miRNAs in the tumor and circulating tumor cells (CTCs) in colon cancer (CC). Methods: Expression of seven miRNAs (hsa-let-7i-5p, hsa-miR-126-5p, hsa-miR-143-3p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-26a-5p, hsa-miR-92a-3p) were determined by real-time PCR in tumors of 200 patients with stage II-IV CC compared with normal colon tissue; levels of CTCs were determined by the CellSearch, and at CTC 〉 3, CTCs were isolated and the expression of the same miRNAs was studied in them. Results: Tumor tissues showed statistically significant (p 〈 0.0005) changes, compared to normal tissues, in the expression of hsa-let-7i-5p (increased by 4.2 times in stage IV), hsa-miR-126-5p (increased by 2.0; 2.1 and 2.9 times in stages II, III and IV, respectively), hsa-miR-143-3p (decreased by 3.3 times in stage IV), hsa-miR-21-5p (increased by 3.9 and 4.8 times in stages III and IV), hsa-miR-25-3p (increased by 3.2 times in stage IV), hsa-miR-26a-5p (decreased by 10.0; 5.0 and 6.7 times in stages II, III and IV, respectively) and hsa-miR-92a-3p (increased by 2.2; 5.1 and 9.5 times in stages II, III and IV, respectively). We observed changes in the expression of hsa-let-7i-5p (increased by 3.4 times), hsa-miR-143-3p (decreased by 3.4 times), hsa-miR-21-5p (increased by 3.2 times) and hsa-miR-92a-3p (increased by 4.3 times) in tumors of patients with stage IV disease, compared to stage II (p 〈 0.005). CTC expression of miRNAs hsa-miR-143-3p, hsa-miR-21-5p, hsa-miR-26a-5p in patients with lymph node metastases, compared to patients without metastases, was decreased by 2.5; 3.6; 5.0 times (p 〈 0.05) respectively, and expression of hsa-miR-92a-3p was elevated by 3.0 times (p 〈 0.05). In patients with liver metastases, CTC expression of hsa-miR-143-3p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-26a-5p was statistically significantly (p 〈 0.05) lower by 4.6; 5.5; 1.7; 5.3 times, respectively, compared to the CTC expression in patients without metastases, and expression of hsa-miR-126-5p and hsa-miR-92a-3p was higher by 2.6 and 5.0 times, respectively, compared to the CTC expression in patients without metastases (p 〈 0.05). CTC expression of hsa-miR-143-3p was 1.8 times lower (p 〈 0.05), and expression of hsa-miR-92a-3p was 1.7 times (p 〈 0.05) higher in patients with distant metastases, compared to patients with regional metastases. Conclusions: On the whole, the miRNA expression profile in the tumor and CTCs in CC were similar, although there were some differences. Tumor tissues in stage IV patients were characterized by overexpression of hsa-let-7i-5p, which is not typical for CTCs. The levels of the tumor suppressor hsa-miR-26a-5p were reduced in tumors of different stages to similar values, but differed in CTCs, which allows differentiation between non-metastatic CC and metastatic CRC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e14511-e14511
    Abstract: e14511 Background: The main effort to improve adoptive cancer immunotherapy is aimed at overcoming the limitations associated with low MHC expression on tumor cells. Reinfusion of patient's ex vivo activated NK cells, which eliminate tumor cells, regardless of the MHC molecules presence on their surface, is among promising approaches. Natural killers fate is regulated by a whole set of cytokines, of which IL-18 and interleukins of the IL-2 family (IL-2, IL-15, IL-7, IL-21) are of particular importance. Despite the common structure of their receptor, interleukins of the IL-2 family may exert different influence on NK phenotype when combined with IL-18. The aim of the study was to investigate the effect of IL-18 combinations with interleukins of IL-2 family on activation markers expression on breast cancer patients’ peripheral blood NK cells. Methods: Peripheral blood NK cells were enriched by magnetic cell sorting from PBMC using the NK Cell Isolation Kit (#130-092-657, Miltenyi Biotec, Germany). Next, the sorted NK were incubated at 10 6 cells/ml in RPMI 1640 medium (Gibco, USA) with addition of cytokines at a concentration of 10 ng/ml in 5 variants: 1) IL-18; 2) IL-18 + IL-2; 3) IL-18 + IL-7; 4) IL-18 + IL-15; 5) IL-18 + IL-21. Cells were further incubated at 5.0% CO 2 and 37 0 C. After 48 hours of incubation, the expression of CD16, CD56 and CD25 markers on NK was assessed by flow cytometry. Results: A decrease in CD16++CD56+ subpopulation percentage up to 52.5% and 54.9% compared to 62.2% in the control was observed after incubation with IL-18 alone and when it was combined with IL-2, respectively. At the same time, the addition of IL-15 and IL-21 caused a further decrease to 38.7% and 39.1%, respectively. Nevertheless the combination of IL-18 and IL-7 led to an increase in CD16++CD56+ subpopulation percentage up to 71.8%. The percentage of CD25-positive NK cells on the whole followed the dynamics of CD16++CD56+ subpopulation with the IL-18 +IL-15 combination causing the maximum decrease (up to 7.6%). The proportion of NK cells with the CD16+CD56++ phenotype, on the contrary, increased after incubation with IL-18 alone and its combination with IL-2 from 34.5% in control to 46.9% and 44.3%, respectively. Interleukin 18 combinations with IL-15 and IL-21 exhibited even more prominent effect causing increase in CD16+CD56++ proportion to 59.6% and 60.4%, respectively. At the same time, incubation with IL-18+IL-7 caused only a slight decrease in the percentage of the CD16++CD56+ NK subpopulation (up to 27.5%). Conclusions: Thus, IL-18 stimulated the generation of the cytokine-producing NK fraction while suppressing the cytolytic fraction. Also the antagonistic effect of IL-7 with IL-18 and the synergistic effect of IL-15 and IL-21 with IL-18 were revealed on NK cells in vitro.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21509-e21509
    Abstract: e21509 Background: The limited range of patients clinically responding to checkpoint inhibitor therapy (CIT) is of interest and requires studying the immunological mechanisms underlying this phenomenon. It also remains to be decided or better clarified which biomarkers should be considered when selecting patients for immunotherapy. The purpose of this study was to evaluate some parameters of the cytokine profiles of peripheral blood in melanoma patients receiving CIT with the disease progression. Methods: The study included 11 patients aged 47-82 years with advanced melanoma. CIT (nivolumab 3 mg/kg once every 14 days or 240 mg once every 14 days) continued until the appearance of reliable signs of the disease progression (in combination with symptomatic deterioration of the patient's condition). The levels of cytokines (TNF-α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ) in the blood serum of patients were determined by ELISA before treatment, after 4 and after 8 injections. The results were expressed as specific content (units/mg). Results: All patients developed disease progression after immunotherapy. CIT was accompanied by different changes most pronounce after the 8 th CIT cycle. Levels of IL-1β, IFN-γ, IL-10 and α-TNF exceeded the values before CIT by 118%, 131%, 84% and 20%, respectively (5.2 [4.37; 6.1] versus 2.0 [0.44;4] , p≤0.041, 3.9 [3.7;4.5] vs. 1.7 [0.5;3.5] , p≤0.021, 6.5 [5.8 ;8.2] vs. 3.5 [3.2;5.4] , p≤0.04; 4.1 [3.9;4.9] vs. 3.4 [ 3.2;3.9] pg/ml, p≤0.047). Levels of IL-6, on the contrary, decreased by the 8th CIT cycle by 32%: 5.1 [3.5; 6.1] versus 7.5 [6.2; 22.3] pg/ml, p≤ 0.045. Levels of IL-2 and IL-8 did not change. Conclusions: The revealed significant increase in levels of IL-1β, IFN-γ, IL-10 and α-TNF, as well as the IL-6 decrease, may indicate certain features of the cytokine profile of melanoma patients during the treatment, which may affect the imbalance of regulatory molecules and contribute to the disease progression.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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