Association of immune-regulatory (FoxP3+)-T-cell tumor infiltration status with benefit from chemoimmunotherapy with gemcitabine, oxaliplatin, 5-FU/FA plus GM-CSF and aldesleukine (GOLFIG) in metastatic colon cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3045-3045
Author(s):  
P. Correale ◽  
P. Tagliaferri ◽  
M. T. Del Vecchio ◽  
C. Remondo ◽  
C. Migali ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Cox Regression ◽  
Treg Cells ◽  
Phase Iii ◽  
Metastatic Colon Cancer ◽  
Tumor Infiltration ◽  
Gm Csf ◽  
Independent Variable

3045 Background: GOLFIG is a novel chemoimmunotherapy regimen, combining gemcitabine, oxaliplatin, 5-FU/FA with immunoadjuvant GM-CSF and aldesleukine, which resulted safe and very active in colon cancer patients. Antitumor activity and immunity feedback to the treatment resulted strictly correlated. The best outcome was observed in patients showing autoimmunity signs, rise in central-memory-T cells, and decline in peripheral and tumor infiltrating immuno-regulatory T (Treg) cells. On these bases, we investigated a possible correlation between Treg tumor infiltration at diagnosis and clinical outcome of these patients. Methods: An immunohistochemistry study was carried out to quantify the infiltration of Treg (FoxP3+) lymphocytes in tumor samples of 41 colon cancer patients who received FOLFOX-4 chemotherapy or GOLFIG chemo-immunotherapy as enrolled in the ongoing phase III GOLFIG-2 trial. Treg tumor infiltration score (range 0 to 5) was then correlated with survival (OS) and time to progression (TTP). Results: A higher Treg tumor infiltration score (score 3–5) was associated to a longer OS and TTP in the whole patient population (high vs low score; TTP=18 vs 9.4 months; p=0.002; OS=55.7 vs 28.9 months; p=0.001); however, those patients with high tumor infiltration of FoxP3+-T cells who received GOLFIG regimen showed the most favorable outcome (high vs low score; TTP=20.8 vs 11.6 months; p=0.04; OS=68.1 vs 41 months; p=0.04). A Cox regression model demonstrated in these patients that a high Treg tumor infiltration score is an independent variable of long survival and prolonged TTP. Conclusions: Our results suggest that GOLFIG chemoimmunotherapy is highly effective in colon carcinoma patients with high FoxP3+ infiltration score and that Treg-tumor infiltration score may be a favorable prognostic marker in colon cancer patients. No significant financial relationships to disclose.

Behavior of Circulating CD4+CD25+Foxp3+ Regulatory T Cells in Colon Cancer Patients Undergoing Surgery

2011 ◽  
Vol 31 (6) ◽  
pp. 1095-1104 ◽  
Author(s):  
Ausilia Sellitto ◽  
Gennaro Galizia ◽  
Umberto De Fanis ◽  
Eva Lieto ◽  
Anna Zamboli ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cancer Patients

scholarly journals Sequential Therapies and the Cost-Effectiveness of Treating Metastatic Colon Cancer Patients

2016 ◽  
Vol 22 (6) ◽  
pp. 628-639 ◽  
Author(s):  
Andinet Woldemichael ◽  
Eberechukwu Onukwugha ◽  
Brian Seal ◽  
Nader Hanna ◽  
C. Daniel Mullins
Keyword(s):  
Colon Cancer ◽  
Cost Effectiveness ◽  
Cancer Patients ◽  
Metastatic Colon Cancer ◽  
The Cost

scholarly journals Development of prognosis model for colon cancer based on autophagy-related genes

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xu Wang ◽  
Yuanmin Xu ◽  
Ting Li ◽  
Bo Chen ◽  
Wenqi Yang
Keyword(s):  
Colon Cancer ◽  
Regression Analysis ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Patient Survival ◽  
Expression Profiles ◽  
Cox Regression Analysis ◽  
Risk Patients

Abstract Background Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied. Methods Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazard models were used to investigate the association between ARG expression profiles and patient prognosis. Results Twenty ARGs were significantly associated with the overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥ 3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 1-, 3-, and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians. Conclusion The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.

scholarly journals he effects of NETosis on fibrinolysis in colon cancer patients

2022 ◽  
Vol 20 (4) ◽  
pp. 25-31
Author(s):  
A. A. Parshina ◽  
N. N. Tsybikov ◽  
P. P. Tereshkov ◽  
T. M. Karavaeva ◽  
M. V. Maksimenya
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Cell Activation ◽  
Fluorescent Microscopy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Metastatic Colon Cancer ◽  
The Given ◽  
Experimental Group ◽  
Pai 1

Aim. To investigate formation of neutrophil extracellular traps (NETs) and their impact on fibrinolysis in patients with colon cancer.Materials and methods. The study was performed in two groups. The experimental group consisted of patients with stage 2–3 non-metastatic colon cancer (n = 17, average age – 67 years). The control group included healthy volunteers matched by sex and age (n = 30, average age – 68 years). An experimental model was created from the whole blood. It included platelet-poor plasma and an isolated culture of neutrophils, previously induced to NETosis by adding 100 nmol PMA. The samples were incubated for 4 hours, then the test tubes were centrifuged to pellet cells and their remnants, and the plasma was transferred for subsequent examination. The plasma incubated with intact neutrophils was used as a control. The levels of interleukin-8 (IL-8) and P-selectin glycoprotein ligand-1 (PSGL-1) were used to determine the degree of cell activation. NETosis was confirmed by enzyme-linked immunosorbent assay (ELISA) and fluorescent microscopy. Fibrinolysis was assessed using the thrombodynamics test. The results were compared with the levels of fibrinolytic system components measured by flow cytometry.Results. In the control group, NETosis induction contributed to pronounced neutrophil activation that was accompanied by an increase in the IL-8, PSGL-1, and plasminogen levels, a decrease in PAI-1, and enhancement of fibrinolysis, compared with the intact samples. Higher levels of IL-8, PSGL-1, plasminogen, and PAI-1 and intensified fibrinolysis were detected in the intact samples. However, PMA-induced NETosis did not result in an increase in the degree of activation and significant changes in the given parameters.Conclusion. NETosis promotes both formation and lysis of fibrin clots. However, in cancer patients, suicidal NETosis does not contribute to fibrinolysis due to intracellular protease depletion, which may be one of the mechanisms causing hypercoagulation and insufficient fibrinolysis in cancer. 

scholarly journals Prognostic and Predictive Value of BGN in Colon Cancer Outcomes and Response to Immunotherapy

2022 ◽  
Vol 11 ◽  
Author(s):  
Zi-Xuan He ◽  
Sheng-Bing Zhao ◽  
Xue Fang ◽  
Ji-Fu E ◽  
Hong-Yu Fu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune Response ◽  
Cancer Patients ◽  
Immune Cells ◽  
Matrix Protein ◽  
Cox Regression ◽  
Extracellular Matrix Protein ◽  
Great Promise ◽  
Clinical Prognosis ◽  
Expression Levels

BackgroundColon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation.MethodsThe differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms.ResultsBGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients.ConclusionBGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.

VEGFR2 expressions in Th1 and CD8+ cytotoxic T lymphocytes (CTL) in colon cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15535-e15535
Author(s):  
Mehmet Artac ◽  
Ayca Ceylan ◽  
Melek Karakurt Eryılmaz ◽  
Murat Araz ◽  
Mustafa Karaagac ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
Cancer Patients ◽  
Study Groups ◽  
T Cell Subsets ◽  
Control Group ◽  
Study Group ◽  
Metastatic Colon Cancer ◽  
Vegf Receptors ◽  
Cancer History

e15535 Background: VEGF receptors have an important role for inhibiting adaptive immun response in colon cancer. Therefore, we analyzed VEGF receptors in circulating T cell subsets according to stage in colon cancer patients. Methods: The prospective study group consisted of 50 patients with histologically confirmed colon cancer and 30 person without any cancer history as a control group. Peripheral blood specimens were collected from the patients after the diagnosis before inducing chemotherapy and radiotherapy. Patients with active infections or autoimmune disorders, who were treated with steroids and antibiotics in the last four weeks before the study enrollment were excluded from the study group. VEGFR2 expressions in circulating T cell subsets (Th1, Th2, Th17, CTL) were analyzed by flow cyctometry. Results: Age and gender were not different between the all study groups. Mean circulating CD4+ folicullar cells were less in colon cancer patients (9.54%±3.99) than the control group (12.03%±4.34), (p < 0.01). Mean circulating CD8+ follicular cells were higher in metastatic colon cancer (n = 26) 2.48% ± 1.68, than the non-metastatic colon cancer patients (n = 24) 1.63% ± 1.37, (p = 0.02). Mean VEGFR2 expressions in Th1 cells were higher in colon cancer patients 248.8 (Mean Flourescein intensity-MFI) than the control group 224.6, (P = 0.006). Mean VEGFR2 expressions in CTL were higher in colon cancer patients (381.8) than the control group (284.7), (p < 0.001). PD-1 expressions were not different between the colon cancer patients and the control group in all circulating T cell subsets. Mean VEGFR2 expressions in Th17 cells were higher non-metastatic colon cancer patients than the metastatic colon cancer patients (326.5 and 268.4 MFI, respectively, p = 0.02). Conclusions: VEGFR2 expressions are increased in circulating Th1 and CTL subsets in colon cancer patients. Whereas PD-1 expressions were not different in circulating T cell subsets than the control. VEGFRs may play an important role for the inhibition of circulating T cell subsets in colon cancer.

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