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Angiogenesis in Hematological Malignancies
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Alida C. Weidenaar, Hendrik J. M. de Jonge, Arja ter Elst, Evelina S. J. M. de Bont
Vasculature of tumors is predominantly formed by angiogenesis, but can also be developed by postnatal vasculogenesis: the formation of new blood vessels from EPCs that differentiate into mature ECs (55). These EPCs are defined as CD34+/CD133+/CD177+/KDR+ cells, which originate in the bone marrow. EPC recruitment and mobilization have been positively correlated with an increase in VEGFA levels; in response to increased VEGFA levels at the site of the tumor, an increase in circulating EPCs was seen (Fig. 2) (56–58). Moreover, CD133+ cells differentiate into mature-type adherent ECs and abolish the CD133 expression in response to VEGFA (59). While it has been shown that these bone marrow–derived EPCs contribute to the tumor vessel formation by incorporating into the endothelium (60), a second group of proangiogenic cells was described; this population, rather than the EPCs, was thought to home in specifically to the tumor and was characterized by the expression of CD45+, TEK+, CD31−, and CD11b+ (61). Inhibition of those cells resulted in a significant reduction of tumor angiogenesis and growth. Finally, the existence of a third proangiogenic population was suggested, which is characterized by CD34, CXCR4 and FLT1 expression and is implicated in the initiation and formation of metastases (62).
Introduction to Myeloproliferative Neoplasms
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
PRV-1 gene is localized to chromosome 19q13.2 and is overexpressed in granulocytes from patients with PV and other non-CML MPNs. Recent studies suggest that PRV-1 and NB1 are alleles of the same gene now referred to as CD177 [47]. Changes in CD177 expression may be a marker of increased or decreased myelopoiesis. Among patients with ET, PRV-1 positivity predicts a significantly higher number of thromboembolic or microcirculatory events [48].
Immune-Related Adverse Events from Cancer Immunotherapy
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Much of the translational research in this field has investigated the potential relationship between irAEs and blood biomarkers as well as cellular repertoire found in irAE tissue histology. Study of the blood and serum have yielded findings regarding the correlation between irAEs and circulating cells, autoantibody presence, and peripheral cytokines and chemokines. Peripheral neutrophil-to-lymphocyte ratios and peripheral eosinophilia at time of event have been associated with ICI toxicities, with the latter closely correlated with dermatologic-irAEs.64 Additionally, peripheral blood gene expression profiling of cases with melanoma and ICI-colitis yielded high levels of CD177 and CEACAM1, two neutrophil-activation markers.65 Regarding the relationship between irAEs and autoantibodies, a systematic review assessing autoantibodies in relation to irAEs found the highest association with ICI-endocrinopathies, dermatologic irAEs, and irAEs affecting the musculature, such as those for myositis / myocarditis / myasthenia gravis.44 A retrospective analysis of patients with non-small-cell lung cancer and PD-1 inhibitor therapy revealed a significant association with “any pre-existing antibody” with that of irAEs and progression-free survival (antibody panel included rheumatoid factor, antinuclear antibody [ANA], antithyroglobulin, and antithyroid peroxidase antibodies).66 In this same vein, there has been notable correlation between pre-ICI anti-GNAL and anti-ITM2B antibodies with that of ICI-hypophysitis as well as pre-ICI anti-CD74 positivity and ICI-pneumonitis.67 A hypothesis-generating proteomic microarray analysis identified an association between severe any-type irAEs and distinct pre-ICI or baseline serum antibody profiles that corresponded to certain immune pathways such as TNF-α signaling or toll-like receptor signaling.68
Novel ligands and modulators of triggering receptor expressed on myeloid cells receptor family: 2015-2020 updates
Published in Expert Opinion on Therapeutic Patents, 2021
Harbinder Singh, Vikrant Rai, Sunil K. Nooti, Devendra K. Agrawal
CD177 antigen is a glycosylphosphatidylinositol-linked N-glycosylated cell surface glycoprotein that was first identified by Lalezari et al. in 1971 in the case of neonatal alloimmune neutropenia and was also found to play a critical role in neutrophil activation [54]. In 2018, Colonna et al. provided evidence of CD177 as an endogenous sTREM-1 binding ligand [55]. To confirm the binding, HEK293 cells (human embryonic kidney cells) transfected with CD177 were incubated with sTREM-1 for 45 minutes followed by immediate analysis. The results revealed the binding of sTREM-1 to HEK293 cells transfected with CD177. Anti-monoclonal antibody (R33) of CD177 blocked the binding of TREM-1 ligands to neutrophils and in vitro inhibited the transendothelial migration of human neutrophils [55].
Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease
Published in Gut Microbes, 2021
Gengfeng Li, Jian Lin, Cui Zhang, Han Gao, Huiying Lu, Xiang Gao, Ruixin Zhu, Zhitao Li, Mingsong Li, Zhanju Liu
Neutrophils are evolutionarily derived from the bone marrow as immediately responsive immune cells, rapidly migrate to the sites of intestinal inflammation and eradicate pathogens through a series of mechanisms including the phagocytosis, degranulation and release of extracellular traps. The exact role of neutrophils during intestinal inflammation is still elusive although both beneficial and detrimental functions have been reported.18 For example, depletion of neutrophils significantly exacerbates TNBS- or CD4+CD45RBhi T cell transfer-induced colitis in mice.16,33 Furthermore, individuals with dysfunction of neutrophils display IBD-like colitis.34 Our previous study has depicted a subset of neutrophils (i.e., CD177+ neutrophils) to have a protective role in the maintenance of mucosal integrity.15 Moreover, our recent work also demonstrated a novel effect of cyclosporine A on neutrophils, showing that cyclosporine A functions as fueling glycolysis and aerobic oxidation to restrain excessive activation, contributing to the induction of clinical remission in acute severe UC patients.35 In contrast, inflamed mucosa from patients with active IBD is infiltrated with large numbers of neutrophils, and the degree of neutrophil infiltration is thought to be instrumental for the assessment of disease activity.17
A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni
Published in Gut Microbes, 2020
Nicholas M Negretti, Yinyin Ye, Lais M Malavasi, Swechha M Pokharel, Steven Huynh, Susan Noh, Cassidy L Klima, Christopher R Gourley, Claude A Ragle, Santanu Bose, Torey Looft, Craig T Parker, Geremy Clair, Joshua N Adkins, Michael E Konkel
We evaluated the proteome from the supernatant of the intestinal loops to further understand the events occurring in the intestine. The proteome of intestinal supernatants was evaluated at 3 and 12 hours after infection, and the data from infected loops were compared to control loops (Supplementary Table 2). Because the initial analysis suggested that neutrophil markers were abundant in the infected loops, we determined the time frame in which the neutrophil specific proteins appeared. We used CD177 as the primary indicator of neutrophil abundance.25 CD177 was not detectable at 3 hours post-infection but was present at 12 hours post-infection in both the loops inoculated with the C. jejuni wild-type strain and the ∆ciaD mutant. Notably, the amount of CD177 was lower in loops inoculated with the ∆ciaD mutant compared to inoculation with the wild-type strain (Figure 5). Additionally, the abundance of CD177 correlated with other neutrophil markers, including matrix metallopeptidase 9 (MMP9), lipocalin 2 (LCN2), elastase (ELANE), and proteinase 3 (PRTN3). These results are consistent with the finding that the C. jejuni wild-type strain causes accumulation of both TNF-α and IL-8 in the intestinal lumen 12 hours post-infection, while the ∆ciaD mutant induces lower concentrations of IL-8. These data demonstrate that neutrophils are recruited to the site of the infection in a manner that is consistent with the ability of C. jejuni to invade cells.