scholarly journals The Protein Secretome Is Altered in Rectal Cancer Tissue Compared to Normal Rectal Tissue, and Alterations in the Secretome Induce Enhanced Innate Immune Responses

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 571
Author(s):  
Aisling B. Heeran ◽  
Margaret R. Dunne ◽  
Maria E. Morrissey ◽  
Croí E. Buckley ◽  
Niamh Clarke ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Cell Biology ◽  
Tissue Injury ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Innate Immune ◽  
Cancer Tissue ◽  
Innate Immune Responses

Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy; however, only ~22% of patients achieve a complete response, and resistance mechanisms are poorly understood. The role of inflammation and immune cell biology in this setting is under-investigated. In this study, we profiled the inflammatory protein secretome of normal (non-cancer) (n = 8) and malignant rectal tissue (n = 12) pre- and post-radiation in human ex vivo explant models and examined the influence of these untreated and treated secretomes on dendritic cell biology (n = 8 for cancer and normal). These resultant profiles were correlated with patient clinical characteristics. Nineteen factors were secreted at significantly higher levels from the rectal cancer secretome when compared to the normal rectal secretome; Flt-1, P1GF, IFN-γ, IL-6, IL-10, CCL20, CCL26, CCL22, CCL3, CCL4, CCL17, GM-CSF, IL-12/IL-23p40, IL-17A, IL-1α, IL-17A/F, IL-1RA, TSLP and CXCL10 (p < 0.05). Radiation was found to have differential effects on normal rectal tissue and rectal cancer tissue with increased IL-15 and CCL22 secretion following radiation from normal rectal tissue explants (p < 0.05), while no significant alterations were observed in the irradiated rectal cancer tissue. Interestingly, however, the irradiated rectal cancer secretome induced the most potent effect on dendritic cell maturation via upregulation of CD80 and PD-L1. Patient’s visceral fat area correlated with secreted factors including CCL20, suggesting that obesity status may alter the tumour microenvironment (TME). These results suggest that radiation does not have a negative effect on the ability of the rectal cancer TME to induce an immune response. Understanding these responses may unveil potential therapeutic targets to enhance radiation response and mitigate normal tissue injury. Tumour irradiation in this cohort enhances innate immune responses, which may be harnessed to improve patient treatment outcome.

scholarly journals High-Resolution Profiling of Innate Immune Responses by Porcine Dendritic Cell Subsets in vitro and in vivo

2020 ◽  
Vol 11 ◽  
Author(s):  
Gaël Auray ◽  
Stephanie C. Talker ◽  
Irene Keller ◽  
Sylvie Python ◽  
Markus Gerber ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
High Resolution ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Dendritic Cell Subsets

Interferon-γ is produced by another player of innate immune responses: The interferon-producing killer dendritic cell (IKDC)

Biochimie ◽  
2007 ◽  
Vol 89 (6-7) ◽  
pp. 872-877 ◽  
Author(s):  
Mathieu Bonmort ◽  
Evelyn Ullrich ◽  
Grégoire Mignot ◽  
Bénédikt Jacobs ◽  
Nathalie Chaput ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Immune Responses ◽  
Interferon Γ ◽  
Innate Immune ◽  
Innate Immune Responses

scholarly journals The Collision of Meta-Inflammation and SARS-CoV-2 Pandemic Infection

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Gabrielle P Huizinga ◽  
Benjamin H Singer ◽  
Kanakadurga Singer
Keyword(s):  
Immune Responses ◽  
Tissue Injury ◽  
Innate Immune ◽  
Organ Injury ◽  
Innate Immune Responses ◽  
Immune Mediators ◽  
Diabetes Status ◽  
The Impact ◽  
Physiologic Role

Abstract The coronavirus disease 2019 (COVID-19) pandemic has forced us to consider the physiologic role of obesity in the response to infectious disease. There are significant disparities in morbidity and mortality by sex, weight, and diabetes status. Numerous endocrine changes might drive these varied responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including hormone and immune mediators, hyperglycemia, leukocyte responses, cytokine secretion, and tissue dysfunction. Studies of patients with severe COVID-19 disease have revealed the importance of innate immune responses in driving immunopathology and tissue injury. In this review we will describe the impact of the metabolically induced inflammation (meta-inflammation) that characterizes obesity on innate immunity. We consider that obesity-driven dysregulation of innate immune responses may drive organ injury in the development of severe COVID-19 and impair viral clearance.

Angiogenic marker associated with resistance to neoadjuvant chemoradiotherapy in rectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11030-11030 ◽  
Author(s):  
Hanjo Kim ◽  
Min Young Lee ◽  
Tae Sung Ahn ◽  
Jina Yun ◽  
Kyoungha Kim ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Growth Factor ◽  
Clinical Stage ◽  
Antiangiogenic Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Angiogenic Factors ◽  
Cancer Tissue ◽  
Expression Rate ◽  
Cancer Tissues

11030 Background: The ability to achieve pathologic down staging after neoadjuvant chemoradiotherapy (CRT) is correlated with improved survival. However, there is no effective method of predicting which patients will response to neoadjuvant CRT. Neoadjuvant CRT can change the expression of angiogenic factors. However, little is known about its possible changes in response to preoperative CRT. We examined the expression of angiogenic factors in rectal cancer tissues before preoperative CRT and after surgery. Methods: Fifty five patients with locally advanced rectal cancer were studied. All patients were given preoperative CRT of 5040 cGy for 5-6 weeks with concurrent administration of 5-fluorouracil and leucovorin. Surgical resection was performed 6–8 weeks later in all patients. Immunohistochemical staining for angiogenenic markers (vascular endothelial growth factor [VEGF], placenta growth factor [PLGF], hypoxia inducible factor 1α [HIF 1α], stromal cell derived factor [SDF 1α]) were performed on specimens obtained before preoperative CRT and after surgery. A semiquantitative-immunohistochemical score established from the extension and intensity of the angiogenic factors was used for analysis. Results: The positive expression rate of VEGF, PLGF, SDF 1α, and HIF 1α was 56.4% (31/55), 65.5% (36/55), 70.9% (39/55), and 47.3% (26/55), respectively. The expression rate of VEGF, PLGF, SDF 1α, and HIF 1α was increased by 3.6% (2/55), 7.3% (4/55), 30.9% (17/55), and 1.8% (1/55) after neoadjuvant CRT, respectively. Expression of VEGF, PLGF, and HIF 1α protein was downregulated after neoadjuvant CRT in the rectal cancer tissues (P < 0.001, P = 0.001, P = 0.044, respectively). However, SDF 1α was upregulated after neoadjuvant CRT (P < 0.001). And also, upregulated expression of SDF 1α after neoadjuvant CRT was significantly associated with resistance to CRT (P = 0.035). However, SDF 1α showed no correlation with other clinical factors (age, sex, clinical stage). Conclusions: Expression of SDF-1α was increased in the rectal cancer tissue after neoadjuvant CRT, as well as has been associated with CRT resistance. Our data suggests that SDF 1α should be evaluated as new target for antiangiogenic therapy.

scholarly journals Alterations in myeloid dendritic cell innate immune responses in the Gαi2-deficient mouse model of colitis

2009 ◽  
Vol 15 (2) ◽  
pp. 248-260 ◽  
Author(s):  
J. A. Peña ◽  
L. Thompson-Snipes ◽  
P. R. Calkins ◽  
N. Tatevian ◽  
M. Puppi ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Mouse Model ◽  
Immune Responses ◽  
Innate Immune ◽  
Myeloid Dendritic Cell ◽  
Deficient Mouse ◽  
Innate Immune Responses

Relations of carcinoembryonic antigen (CEA) staining of cancer tissue and serum CEA levels to histologic response in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (nCRT).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 790-790
Author(s):  
Gota Saito ◽  
Sotaro Sadahiro ◽  
Hiroshi Miyakita ◽  
Kazutake Okada ◽  
Akira Tanaka ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Shrinkage Rate ◽  
Tumor Regression Grade ◽  
Cancer Tissue ◽  
Tumor Shrinkage ◽  
Histologic Response ◽  
Serum Cea

790 Background: Neoadjuvant chemoradiotherapy (nCRT) is a standard of care for LARC. The serum CEA level is a predictor of the response to nCRT; however, the relation between CEA production immunohistochemically evaluated in cancer tissue and treatment response remains unclear. Methods: The study group comprised 145 patients with clinical Stage II/III rectal cancer who received nCRT followed by surgery from 2005 through 2013. The radiation dose was 40 to 45 Gy. UFT- or S-1-based chemotherapy was given concurrently. Surgery was performed 6 to 8 weeks after the completion of radiotherapy. Immunohistological CEA staining patterns in biopsy tissue obtained before nCRT were evaluated. Specimens in which the luminal cell membrane or the cytoplasm was strongly stained were defined as staining positive. The histologic response was evaluated on the basis of the pathological complete response (ypCR) rate, T downstaging, tumor regression grade (TRG), and tumor shrinkage rate on MRI. Results: CEA staining in biopsy specimens and serum CEA levels were both negative in 17 patients (11.7%) and both positive in 72 patients (49.7%). There was no relation between the groups (p = 0.174). In patients with negative CEA staining, the rates of ypCR, T downstaging, marked regression, and mean tumor shrinkage were 24.3%, 51.4%, 45.9%, and 72.3%, respectively. In patients with positive CEA staining, these rates were 11.1%, 48.1%, 37.0%, and 72.8%, respectively. CEA staining of cancer tissue was not significantly related to the ypCR rate, T downstaging, a marked regression rate, or the tumor shrinkage rate on MRI (p = 0.060, p = 0.849, p = 0.436, and p = 0.874, respectively). Patients with negative serum CEA levels before nCRT had significantly higher rates of ypCR, T downstaging, marked regression, and tumor shrinkage on MRI than did patients with positive serum CEA levels (p = 0.014, p = 0.006, p = 0.002, and p = 0.014, respectively). Conclusions: Serum CEA levels before nCRT were a significant predictor of the histologic response to nCRT; in contrast, tissue CEA staining before nCRT was unrelated to the histologic response to nCRT.

PS3-06 Differences in magnitude and timing of human monocyte derived dendritic cell innate immune responses to two strains of respiratory syncytial virus

Cytokine ◽  
2010 ◽  
Vol 52 (1-2) ◽  
pp. 83
Author(s):  
Philippa Hillyer ◽  
Aaron Chen ◽  
Lynnsie M. Schramm ◽  
Viraj P. Mane ◽  
Maria Navarro ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Human Monocyte ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Syncytial Virus

The Emerging Role of B Lymphocytes in Cardiovascular Disease

2020 ◽  
Vol 38 (1) ◽  
pp. 99-121
Author(s):  
Luigi Adamo ◽  
Cibele Rocha-Resende ◽  
Douglas L. Mann
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Biology ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Review Of The Literature ◽  
Adaptive Immune

B cells are traditionally known for their ability to produce antibodies in the context of adaptive immune responses. However, over the last decade B cells have been increasingly recognized as modulators of both adaptive and innate immune responses, as well as players in an important role in the pathogenesis of a variety of human diseases. Here, after briefly summarizing our current understanding of B cell biology, we present a systematic review of the literature from both animal models and human studies that highlight the important role that B lymphocytes play in cardiac and vascular disease. While many aspects of B cell biology in the vasculature and, to an even greater extent, in the heart remain unclear, B cells are emerging as key regulators of cardiovascular adaptation to injury.

scholarly journals Immune regulation in renal inflammation

2021 ◽  
Author(s):  
Katrin Neumann ◽  
Gisa Tiegs
Keyword(s):  
Immune Responses ◽  
Immune Regulation ◽  
Immune Cell ◽  
Tissue Injury ◽  
Renal Tissue ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Renal Inflammation ◽  
Immune Mediated ◽  
Toxic Drugs

AbstractRenal inflammation, induced by autoantigen recognition or toxic drugs, leads to renal tissue injury and decline in kidney function. Recent studies have demonstrated the crucial role for regulatory T cells in suppressing pathogenic adaptive but also innate immune responses in the inflamed kidney. However, there is also evidence for other immune cell populations with immunosuppressive function in renal inflammation. This review summarizes mechanisms of immune cell regulation in immune-mediated glomerulonephritis and acute and chronic nephrotoxicity.

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