Correlation of IL-17 with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 83-83 ◽  
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Daisuke Ujiie ◽  
Mai Ashizawa ◽  
Tomohiro Kikuchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Suppression ◽  
Stimulation Index ◽  
Suppressor Cells ◽  
Retinol Binding Protein ◽  
Reactive Protein ◽  
Th 17 ◽  
Cell Mediated Immune Response ◽  
Inflammatory Processes ◽  
Advanced Stages

83 Background: Although a causal relationship linking inflammation and cancer immunity is more widely accepted today, precise cell mechanisms mediating this relationship have not been elucidated. IL-17, a pro-inflammatory cytokine primarily secreted by T helper (Th)17 cells, has previously been associated with inflammatory processes in autoimmune disease. The presence of IL-17 and Th17 cells has been confirmed in various invasive cancers and recently linked to immunosuppression in cancer patients. We investigated systemic inflammation, immune suppression, malnutrition, and prognosis associated with IL-17 in patients with gastric and colorectal cancer. Methods: We measured IL-17 in 106 patients, including 43 with gastric and 63 with colorectal cancer, Production of IL-17 stimulated by PHA was measured by ELISA. MDSC (myeloid-derived suppressor cells), which significantly contribute to immunosuppression, were measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and the SI (stimulation index) of lymphocytes’ blastogenic response were used as markers of cell-mediated immune response. Results: Production of IL-17 increased in advanced stages of gastric and colorectal cancer. IL-17 positively correlated with levels of MDSC, serum concentrations of VEGF, NLR, and levels of CRP, and was inversely correlated with IL-12 production, SI, and nutritional markers including prealbumin and retinol binding protein. Patient cohorts were divided into two groups with IL-17 level (540 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer both significantly worse in patients with high production of IL-17 than in those with low IL-17, although the differences were not significant in patients at stages I and II. Conclusions: The present study suggests that IL-17 may reflect an inflammatory impact on the advancement and progression of cancer, and it may serve as useful marker of immune suppression involving MDSC, malnutrition, and poor prognosis in patients with gastric and colorectal cancer.

Correlation of VEGF with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Daisuke Ujiie ◽  
Mai Ashizawa ◽  
Hirokazu Okayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Suppression ◽  
Stimulation Index ◽  
Suppressor Cells ◽  
Serum Levels ◽  
Retinol Binding Protein ◽  
Vascular Permeability Factor ◽  
Reactive Protein ◽  
Cell Mediated Immune Response ◽  
Immunosuppressive Cells

582 Background: Although a causal relationship for inflammation and immunity of cancer is more widely accepted today, the precise cell mechanisms mediating this relationship have not been elucidated. Vascular endothelial growth factor (VEGF), previously known as vascular permeability factor. 45 kDa protein, belongs to a family of platelet-derived growth factors. VEGF, inflammation-related protein, could contribute to the accumulation of immunosuppressive cells (MDSC, Treg, TAM, and Tie-2-expressingmonocytes) in tumor-bearing hosts through direct or indirect mechanisms. Methods: We tested the serum levels of VEGF by ELISA in 106 patients including 43 with gastric and 63 with colorectal cancer, and they were increased in advanced stages of gastric and colorectal cancer. Production of IL-17, pro-inflammatory cytokine, with a stimulation of PHA was measured by ELISA and MDSC (myeloid-derived suppressor cells), one of major immunosuppressing cells, was measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and SI (stimulation index) of blastogenic response of lymphocytes were used as markers of cell-mediated immune response. Results: The concentrations of VEGF were positively correlated with levels of MDSC, production of IL-17, NLR and CRP, and were inversely correlated with IL-12 production, SI and nutritional markers including prealbumin and retinol binding protein. The patients were both divided into two groups with a serum level of VEGF (330 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer were both significantly worse in patients with high levels of VEGF than in those with low VEGF although the differences were not significant in patients with stagesⅠand II. Conclusions: The results of the present study suggested that VEGF may have an impact on advancement and progression involving inflammation and serve as useful markers of the immune suppression involving MDSC, malnutrition and poor prognosis in patients with gastric and colorectal cancer.

scholarly journals IL-17 and VEGF are increased and correlated to systemic inflammation, immune suppression, and malnutrition in patients with breast cancer

2017 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Kazunoshin Tachibana ◽  
Masahiko Shibata ◽  
Kenji Gonda ◽  
Yoshiko Matsumoto ◽  
Takahiro Nakajima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Function ◽  
Systemic Inflammation ◽  
Immune Suppression ◽  
Stimulation Index ◽  
Suppressor Cells ◽  
Serum Levels ◽  
Retinol Binding Protein ◽  
Cell Mediated Immunity ◽  
The Status

Relationships between inflammation and innate immunity in cancer are widely accepted today; however, the precise cell mechanisms mediating these relationships have not yet been elucidated. Interleukin (IL)-17 is a proinflammatory cytokine that has been reported to induce inflammation in patients with autoimmune diseases. Myeloid-derived suppressor cells (MDSC) may contribute to the negative regulation of immune responses during cancer and inflammation. Vascular endothelial growth factor (VEGF) is reported to have multiple biological actions including increasing vascular permeability, neovascularization, and possible inhibition of immune function in malignant diseases. This study investigated the status of systemic inflammation and immune suppression associated with IL-17 and VEGF in patients with breast cancer. IL-17 production and the serum levels of VEGF were also increased in advanced stages of the disease. The production of IL-12, which induces Th1 cells, and the stimulation index (SI), which is a marker of cell-mediated immune function, were both shown to decrease along with disease advancement. Also, the production of IL-17 and the VEGF levels were both positively correlated with the levels of MDSC, the neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and were inversely correlated with IL-12 production and the SI. Nutritional markers, including prealbumin (PA), transferrin (TF), and retinol-binding protein (RBP), were also shown to be significantly lower in patients with high production of IL-17 or high levels of VEGF. These data clearly showed that IL-17 and VEGF, whose levels correlated with each other and with those of MDSC, were significantly associated with disease advancement, systemic inflammation, suppression of cell-mediated immunity including Th1 induction, and malnutrition.

Correlation of inflammation-related markers with MDSC and IL-17, and use as prognostic indicators in patients with advanced gastric and colorectal cancers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14204-e14204
Author(s):  
Masahiko Shibata ◽  
Daisuke Ujiie ◽  
Mai Ashizawa ◽  
Tomohiro Kikuchi ◽  
Hirokazu Okayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Markers ◽  
Mononuclear Cells ◽  
Suppressor Cells ◽  
Prognostic Indicators ◽  
Peripheral Blood Mononuclear ◽  
Patients With Cancer ◽  
Kaplan Meier ◽  
Th 17 ◽  
Advanced Stages

e14204 Background: Although a causal relationship for inflammation and immunity of cancer is more widely accepted today, the precise cell mechanisms mediating this relationship have not been elucidated. Accumulating evidence suggests that myeloid-derived suppressor cells (MDSC), may contribute to the negative regulation of immune responses during cancer and inflammation. IL-17 is a pro-inflammatory cytokine that is primarily secreted by T helper (Th)17 cells and we have reported that IL-17 correlates with immunosuppressive conditions in patients with cancer. Methods: PBMC (peripheral blood mononuclear cells) were harvested from 106 patients including 43 with gastric and 63 with colorectal cancer. PBMC were stimulated with PHA (phytohemagglutinin) and the production of IL-17 was measured by ELISA. MDSC were detected by flow cytometry (CD11b+,CD14-,CD33+). The levels of CRP (C-reacting protein) and NLR (neutrophil to lymphocyte ratio) were used as inflammatory markers. Results: Both of MDSC and IL-17 production were increased in patients with advanced stages, and correlated with each other, inflammatory markers and immune suppression. The patients were divided with average levels of MDSC and IL-17 production and the prognosis were analyzed with Kaplan-Meier method. The overall survival of patients with high MDSC or high IL-17 production were significantly worse than those with low MDSC or low IL-17 production, respectively, in patients with stages III and IV, although the differences were not significant in patients with stages I and II. Conclusions: Thus these inflammatory markers are closely related with systemic inflammation involving IL-17 and with immunosuppression driven by MDSC, and are effective prognostic indicators in patients with stages III and IV gastric and colorectal cancer.

Correlation of production of IL-17 with immune suppression relating myeloid-derived suppressor cells (MDSC) and nutritional damages in patients with digestive system cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 437-437
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Takashi Yazawa ◽  
Rei Yashima ◽  
Takashi Kimura ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Immune Suppression ◽  
Th17 Cells ◽  
Digestive System ◽  
Suppressor Cells ◽  
Digestive Cancer ◽  
Cellular Mechanisms ◽  
Neutrophil Lymphocyte Ratio ◽  
Cell Mediated Immune Response ◽  
Inflammatory Bowel

437 Background: Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cellular mechanisms mediating this relationship remain unclear. Th17 cells, which produce the proinflammatory cytokine IL-17, have been recognized as one of the key factors in regulation of inflammatory bowel disease and rheumatoid arthritis. Methods: This study demonstrated that, in patients with digestive system cancers including 7 patients with esophageal, 14 with gastric, 20 with colorectal, 5 with hepatocellular, 7 with cholangiocellular, and 7 with pancreatic carcinomas, IL-17 production was correlated with MDSC level and with markers for nutritional impairment, immune suppression and chronic inflammation. Results: IL-17 production was significantly higher in patients with all types of digestive cancer than in normal volunteers. In addition, IL-17 production levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio, and significantly inversely correlated with cell mediated immune response indicators (lymphocyte PHA-blastogenesis and IL-12 production) and patients’ nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. Conclusions: These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism for disease progression through enhancement of immune suppression or cachexia. Controlling activation of Th17 cells may prove to be a valuable strategy for treatment of patients with gastrointestinal cancer.

scholarly journals Sex, Type of Surgery, and Surgical Site Infections Are Associated with Perioperative Cortisol in Colorectal Cancer Patients

2021 ◽  
Vol 10 (4) ◽  
pp. 589
Author(s):  
Mariusz G. Fleszar ◽  
Paulina Fortuna ◽  
Marek Zawadzki ◽  
Paweł Hodurek ◽  
Iwona Bednarz-Misa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Open Surgery ◽  
Surgical Site Infections ◽  
Time Profile ◽  
C Reactive Protein ◽  
Robot Assisted ◽  
Related Factors ◽  
Reactive Protein ◽  
Baseline Cortisol ◽  
Colorectal Cancer Patients

Excessive endocrine response to trauma negatively affects patients’ well-being. Cortisol dynamics following robot-assisted colorectal surgery are unknown. We aimed at determining the impact of cancer pathology and surgery-related factors on baseline cortisol levels and analyzed its time-profile in colorectal cancer patients undergoing open or robot-assisted surgery. Cortisol levels were measured using liquid chromatography quadrupole time-of-flight mass spectrometry. Baseline cortisol was not associated with any patient- or disease-related factors. Post-surgery cortisol increased by 36% at 8 h and returned to baseline on postoperative day three. The cortisol time profile was significantly affected by surgery type, estimated blood loss, and length of surgery. Baseline-adjusted cortisol increase was greater in females at hour 8 and in both females and patients from open surgery group at hour 24. Solely in the open surgery group, cortisol dynamics paralleled changes in interleukin (IL)-1β, IL-10, IL-1ra, IL-7, IL-8 and tumor necrosis factor (TNF)-α but did not correlate with changes in IL-6 or interferon (IFN)-γ at any time-point. Cortisol co-examined with C-reactive protein was predictive of surgical site infections (SSI) with high accuracy. In conclusion, patient’s sex and surgery invasiveness affect cortisol dynamics. Surgery-induced elevation can be reduced by minimally invasive robot-assisted procedures. Cortisol and C-reactive protein as SSI biomarkers might be of value in the evaluation of safety of early discharge of patients.

Lymphocyte C-reactive protein ratio: A new biomarker to predict early complications after gastrointestinal oncologic surgery

2021 ◽  
pp. 1-9
Author(s):  
Murat Yildirim ◽  
Bulent Koca
Keyword(s):  
Colorectal Cancer ◽  
Postoperative Complications ◽  
Inflammatory Markers ◽  
Operation Time ◽  
C Reactive Protein ◽  
Oncologic Surgery ◽  
Protein Ratio ◽  
Colorectal Cancer Surgery ◽  
Neutrophil Lymphocyte Ratio ◽  
Reactive Protein

BACKGROUND: Lymphocyte-to-C-reactive protein ratio (LCR) has been used as a post-surgical prognostic biomarker in patients with gastric and colorectal cancer. However, its relationship with early postoperative complications in these patients is unknown. In this study, we aimed to reveal the relationship between LCR and postoperative complications. METHODS: Eighty-one patients operated for stomach and colorectal cancer between January 2020 and August 2020 were prospectively analyzed. On preoperative and postoperative days 1, 3 and 5, other inflammatory parameters, mainly LCR, neutrophil lymphocyte ratio (NLR), were recorded. The patients were divided into two groups according to Clavien-Dindo classification as stage III and higher complications major, stage I-II/non-complication minor. RESULTS: Fifty seven patients were operated for colorectal cancer, 24 patients for gastric cancer. The mean age of the patients was 65.6 ± 12.6, 34.6% of them was women. Age, operation time and hospital stay were significantly different between the groups (p= 0.004, p= 0.002, p< 0.001). Major complications developed in 18 patients. On postoperative day 5, LCR found superior diagnostic accuracy in predicting major postoperative complications compared to other inflammatory markers. On the postoperative 5th day, the cut-off value of LCR was 0.0034, 88.8% (71.9–94.8) sensitivity, and 85.7% (73.6–95.4) selectivity. CONCLUSION: Among different inflammatory markers, postoperative LCR is a safe and effective predictor of postoperative complications, especially after gastric and colorectal cancer surgery on day 5.

scholarly journals Inhibition of CCL7 derived from Mo-MDSCs prevents metastatic progression from latency in colorectal cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xiaoli Ren ◽  
Jianbiao Xiao ◽  
Wanning Zhang ◽  
Feifei Wang ◽  
Yongrong Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Suppressor Cells ◽  
Metastatic Progression ◽  
Ht29 Cells ◽  
Metastatic Cells ◽  
Long Time ◽  
Mice Liver ◽  
Short Time ◽  
Related Proteins

AbstractIn colorectal cancer (CRC), overt metastases often appear after years of latency. But the signals that cause micro-metastatic cells to remain indolent, thereby enabling them to survive for extended periods of time, are unclear. Immunofluorescence and co-immunoprecipitation assays were used to explore the co-localization of CCL7 and CCR2. Immunohistochemical (IHC) assays were employed to detect the characters of metastatic HT29 cells in mice liver. Flow cytometry assays were performed to detect the immune cells. Bruberin vivo MS FX Pro Imager was used to observe the liver metastasis of CRC in mice. Quantitative real-time PCR (qRT-PCR) and western blot were employed to detect the expressions of related proteins. Trace RNA sequencing was employed to identify differentially expressed genes in MDSCs from liver micro-M and macro-M of CRC in mice. Here, we firstly constructed the vitro dormant cell models and metastatic dormant animal models of colorectal cancer. Then we found that myeloid-derived suppressor cells (MDSCs) were increased significantly from liver micro-metastases to macro-metastases of CRC in mice. Moreover, monocytic MDSCs (Mo-MDSC) significantly promoted the dormant activation of micro-metastatic cells compared to polymorphonuclear MDSCs (PMN-MDSC). Mechanistically, CCL7 secreted by Mo-MDSCs bound with membrane protein CCR2 of micro-metastatic cells and then stimulated the JAK/STAT3 pathway to activate the dormant cells. Low-dose administration of CCL7 and MDSCs inhibitors in vivo could significantly maintain the CRC metastatic cells dormant status for a long time to reduce metastasis or recurrence after radical operation. Clinically, the level of CCL7 in blood was positively related to the number of Mo-MDSCs in CCR patients, and highly linked with the short-time recurrence and distant metastasis. CCL7 secreted by Mo-MDSCs plays an important role in initiating the outgrowth of metastatic latent CRC cells. Inhibition of CCL7 might provide a potential therapeutic strategy for the prevention of metastasis recurrence.

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