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Diverse macrophages polarization in tumor microenvironment
Inmoo Rhee 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.11
Macrophages are traditional innate immune cellsthat play critical roles in the clearance of pathogens and themaintenance of tissue homeostasis. Accumulating evidenceproves that macrophages affect cancer initiation andmalignancy. Macrophages can be categorized into twoextreme subsets, classically activated (M1) and alterna-tively activated (M2) macrophages based on their distinctfunctional abilities in response to microenvironmentalstimuli. In a tumor microenvironment, tumor associatedmacrophages (TAMs) are considered to be of the polarizedM2 phenotype that enhances tumor progression and rep-resent a poor prognosis. Furthermore, TAMs enhancetumor angiogenesis, growth, metastasis, and immunosup-pression by secreting a series of cytokines, chemokines,and proteases. The regulation of macrophage polarizationis considered to be a potential future therapy for cancermanagement.
( Ji In Ryu ),( Seo Ri Wui ),( Ara Ko ),( Hien Thi Thu Do ),( Yeon Jeong Lee ),( Hark Jun Kim ),( Inmoo Rhee ),( Shin Ae Park ),( Kwang Sung Kim ),( Yang Je Cho ),( Na Gyong Lee ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.8
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that commonly causes fatal infections in cystic fibrosis and burn patients as well as in patients who are hospitalized or have impaired immune systems. P. aeruginosa infections are difficult to treat owing to the high resistance of the pathogen to conventional antibiotics. Despite several efforts, no effective prophylactic vaccines against P. aeruginosa are currently available. In this study, we investigated the activity of the CIA06 adjuvant system, which is composed of alum and de-Oacylated lipooligosaccharide, on a P. aeruginosa outer membrane protein (OMP) antigen vaccine in mice. The results indicated that CIA06 significantly increased the antigen-specific IgG titers and opsonophagocytic activity of immune sera against P. aeruginosa. In addition, the antibodies induced by the CIA06-adjuvanted vaccine exhibited higher cross-reactivity with heterologous P. aeruginosa strains. Finally, mice immunized with the CIA06-adjuvanted vaccine were effectively protected from lethal P. aeruginosa challenge. Based on these data, we suggest that the CIA06 adjuvant system might be used to promote the immunogenicity and protective efficacy of the P. aeruginosa OMP vaccine.
( Ara Ko ),( Seo Ri Wui ),( Ji In Ryu ),( Yeon Jeong Lee ),( Do Thi Thu Hien ),( Inmoo Rhee ),( Sung Jae Shin ),( Shin Ae Park ),( Kwang Sung Kim ),( Yang Je Cho ),( Na Gyong Lee ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.1
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Bacillus Calmette-Guerin (BCG) vaccine is the only TB vaccine currently available, but it is not sufficiently effective in preventing active pulmonary TB or adult infection. With the purpose of developing an improved vaccine against TB that can overcome the limitations of the current BCG vaccine, we investigated whether adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS) are capable of enhancing the immunogenicity and protective efficacy of TB subunit vaccines. The results revealed that the dLOS/dimethyl dioctadecyl ammonium bromide (DDA) adjuvant formulation significantly increased both humoral and Th1-type cellular responses to TB subunit vaccine that are composed of three antigens, Ag85A, ESAT-6, and HspX. The adjuvanted TB vaccine also effectively induced the Th1-type response in a BCG-primed mouse model, suggesting a potential as a booster vaccine. Finally, the dLOS/DDA-adjuvanted TB vaccine showed protective efficacy against M. tuberculosis infection in vitro and in vivo. These data indicate that the dLOS/DDA adjuvant enhances the Th1-type immunity and protective efficacy of the TB subunit vaccine, suggesting that it would be a promising adjuvant candidate for the development of a booster vaccine.
SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin
Chen, Jun,Zhong, Ming-Chao,Guo, Huaijian,Davidson, Dominique,Mishel, Sabrin,Lu, Yan,Rhee, Inmoo,Pé,rez-Quintero, Luis-Alberto,Zhang, Shaohua,Cruz-Munoz, Mario-Ernesto,Wu, Ning,Vinh, Donald C.,Si Nature Publishing Group 2017 Nature Vol. No.
<P>Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors(1,2). Phagocytosis by macrophages plays a critical role in cancer control(3-6). Therapeutic blockade of signal regulatory protein (SIRP)-alpha, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo(7-10), suggesting that blockade of the SIRP alpha-CD47 checkpoint could be useful in treating human cancer(11-14). However, the prophagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely unknown. Here we find that macrophages are much more efficient at phagocytosis of haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in response to SIRP alpha-CD47 blockade. Using a mouse lacking the signalling lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell-specific receptors, we determined that phagocytosis of haematopoietic tumour cells during SIRP alpha-CD47 blockade was strictly dependent on SLAM family receptors in vitro and in vivo. In both mouse and human cells, this function required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319), expressed on macrophages and tumour cell targets. In contrast to most SLAM receptor functions(15-17), SLAMF7-mediated phagocytosis was independent of signalling lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18-20) and utilize signals involving immunoreceptor tyrosine-based activation motifs(21,22). These findings elucidate the mechanism by which macrophages engulf and destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor-independent function for a SLAM receptor. Lastly, they suggest that patients with tumours expressing SLAMF7 are more likely to respond to SIRP alpha-CD47 blockade therapy.</P>