Review
Pharmacology & Pharmacy
Srijan Dubey, Sayak Ghosh, Debosmita Goswami, Debapriya Ghatak, Rudranil De
Summary: Macrophages are immune cells that can engulf and destroy target cells, including tumor cells. Some macrophages undergo a change to become polarized M2 macrophages while devouring cancer cells. M2 macrophages play important roles in metastasis, tumor suppression, and angiogenesis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Cell Biology
Yanyu Jiang, Lihui Li, Yan Li, Guangwei Liu, Robert M. Hoffman, Lijun Jia
Summary: The neddylation pathway regulates the function, migration, survival, and polarization of macrophages, highlighting its implications for cancer therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Chizumi Abe, Maharshi Bhaswant, Teruo Miyazawa, Taiki Miyazawa
Summary: Cancer is characterized by the rapid growth and spread of aberrant cells, leading to metastasis. Widespread metastases are the main cause of death in cancer patients. Different types of cancer cells vary in their proliferation and response to treatment, and conventional drugs often have harmful side effects. Utilizing exosomes as drug carriers for targeted therapy and regulating macrophage polarization in the tumor microenvironment show promise as natural and harmless approaches to cancer treatment.
Review
Immunology
Jiashu Han, Luochu Dong, Mengwei Wu, Fei Ma
Summary: Immunotherapy has revolutionized tumor treatment, but many patients still do not respond due to the immunosuppressive tumor microenvironment. Tumor-associated macrophages (TAMs) play a crucial role in shaping this microenvironment and interacting with intratumoral T cells. However, the heterogeneity and plasticity of TAMs make it challenging to target specific factors and develop effective therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Hao Wang, Jinwen Yin, Yuntian Hong, Anli Ren, Haizhou Wang, Mengting Li, Qiu Zhao, Congqing Jiang, Lan Liu
Summary: In this study, the researchers found that SCG2 expression was significantly decreased in CRC tumor tissues and differentially distributed between tumor and adjacent normal tissues. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate tumor immunity by influencing immune cell infiltration and macrophage polarization in CRC.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Maria Rosaria Galdiero, Ilaria Mormile, Francescopaolo Granata, Stefania Loffredo, Aikaterini Detoraki, Francesca Della Casa, Maria Luisa Trocchia, Annagioia Ventrici, Amato de Paulis, Francesca Wanda Rossi
Summary: Cancer-related inflammation plays an important role in tumor initiation and progression. Tumor-associated macrophages (TAMs) have plasticity and can contribute in different ways to carcinogenesis. Secreted phospholipase A(2) enzymes (sPLA(2)s) have multiple biological effects on cancer-related inflammation.
Article
Biochemistry & Molecular Biology
Ksenija Korotkaja, Juris Jansons, Karina Spunde, Zhanna Rudevica, Anna Zajakina
Summary: Reprogramming TAMs is a promising strategy for cancer immunotherapy. In this study, a new 3D model was established to investigate macrophage programming in the presence of cancer cell spheroids. The findings showed that the profile of cytokines, chemokines, and surface markers of 3D-cultured macrophages did not differ conceptually from monolayer-cultured M1 and M2-programmed macrophages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Xintong Zhou, Xiaomin Wang, Qi Sun, Wenfeng Zhang, Cun Liu, Wenzhe Ma, Changgang Sun
Summary: This paper discusses the infiltration and polarization effects of natural compounds on lung cancer tumor-associated macrophages (TAMs), provides a detailed classification and systematic review of natural compounds, and summarizes the bias of different kinds of natural compounds by affecting their antitumor mechanism of TAMs, with the aim of providing new perspectives and potential therapeutic drugs for targeted macrophages in the treatment of lung cancer.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Nanoscience & Nanotechnology
Adityanarayan Mohapatra, Santhosh Kalash Rajendrakumar, Gopalakrishnan Chandrasekaran, Vishnu Revuri, Padmanaban Sathiyamoorthy, Yong-Kyu Lee, Jae Hyuk Lee, Seok-Yong Choi, In-Kyu Park
Summary: A peroxidase-mimicking nanoscavenger was developed to block the secretion of reactive oxygen species (ROS) and proinflammatory cytokines in gouty arthritis induced by monosodium urate (MSU) crystals. The nanoparticles alleviated joint swelling by abrogating ROS and inflammatory cytokine secretions from proinflammatory macrophages, preventing neutrophil infiltration and fluid buildup at the inflammation site. The treatment also reduced macrophage and neutrophil influx in the injured region in zebrafish and mouse models. Overall, the strategy of using biomineralized nanoscavengers shows clinical significance in dual blocking of peroxides and COX2 to prevent inflammation cell influx.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Review
Immunology
Zicong He, Shuixing Zhang
Summary: TAMs are crucial immune cells in tumors, and their functional transformation from M1 to M2 as tumors progress plays a key role in immunosuppression and tumor promotion processes. Understanding the mechanism of TAM functional transformation in the hypoxic environment is essential for developing novel tumor immunotherapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Hui Wang, Tian Tian, Jinhua Zhang
Summary: Colorectal cancer (CRC) is a highly prevalent and lethal malignant tumor in the digestive system. Tumor-associated macrophages (TAMs) play a crucial role in various mechanisms of CRC progression, such as promoting tumor proliferation, invasion, angiogenesis, and immunosuppression, although their exact role is still debated in clinical evidence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Changhe Hou, Ming Lu, Zixiong Lei, Shuangwu Dai, Wei Chen, Shaohua Du, Qinglin Jin, Zhongxin Zhou, Haomiao Li
Summary: This study found that high mobility group box 1 (HMGB1) is overexpressed in osteosarcoma tissues and is positively correlated with AJCC III and IV stages, lymph node metastasis, and distant metastasis. HMGB1 regulates macrophage polarization through the receptor RAGE. Polarized M2 macrophages induce osteosarcoma migration and invasion, activating HMGB1 expression in osteosarcoma cells to form a positive feedback regulation.
LABORATORY INVESTIGATION
(2023)
Article
Oncology
Jie Huang, Mengyao Zheng, Yan Li, Dingwei Xu, Daguang Tian
Summary: This study found that DLGAP5 is upregulated in gallbladder cancer (GBC) and is strongly associated with poor prognosis in GBC patients. DLGAP5 promotes the proliferation, migration, and M2 polarization of GBC cells through the cAMP pathway, providing a theoretical basis for the treatment of GBC and potentially serving as a promising therapeutic target.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Immunology
Qin Hu, Gujie Wu, Runtian Wang, Huiyun Ma, Zhouwei Zhang, Qun Xue
Summary: This article provides a systematic review on the mechanism of tumor-associated macrophages (TAM) polarization, therapeutic strategies, and the biological functions of Tim-3 positive macrophages, aiming to provide new insights into the pathogenesis and treatment of lung cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Holly J. Hulsebus, Kevin M. Najarro, Rachel H. McMahan, Devin M. Boe, David J. Orlicky, Elizabeth J. Kovacs
Summary: Alcohol consumption increases the risk of infections, particularly pneumococcal pneumonia. Pneumonia patients with alcohol use require more intensive treatment and longer hospital stays. Alcohol consumption affects the immune response in the respiratory tract.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alexandra De Zutter, Luna Dillemans, Nele Berghmans, Sam Noppen, Helena Crijns, Paulien Verscheure, Janne Verhaegen, Erik Martens, Lotte Vanbrabant, Noemie Portner, Dominique Schols, Paul Proost, Sofie Struyf
Summary: Glycosaminoglycans/proteoglycans (GAGs/PGs) play a crucial role in regulating tumor progression and can be potential targets for anti-cancer therapy. A D-amino acid version of CXCL9(74-103), called D-CXCL9(74-103), showed anti-angiogenic properties and inhibited endothelial spheroid sprouting and vessel formation. D-CXCL9(74-103) also exhibited anti-tumoral activity against heparan sulfate high B16-BL6 melanoma cells but had no effect on chondroitin sulfate high HCT116 colon carcinoma cells. These findings highlight the importance of tumor-associated GAGs in adhesion and metastasis and suggest the potential of D-CXCL9(74-103) as a therapeutic agent for heparan sulfate high tumors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Sarah Thompson, Chong Yun Pang, Krishna Mohan Sepuru, Seppe Cambier, Thomas P. Hellyer, Jonathan Scott, A. John Simpson, Paul Proost, John A. Kirby, Krishna Rajarathnam, Neil S. Sheerin, Simi Ali
Summary: Chemokine CXCL8 plays a crucial role in human immune response by mediating neutrophil migration and activation at sites of infection and injury. This study demonstrates that peroxynitrite can nitrate CXCL8, leading to impaired neutrophil migration and activation. The nitrated chemokine showed reduced ability to induce neutrophil migration in vitro and failed to promote leukocyte recruitment in vivo due to impaired receptor signaling and binding to glycosaminoglycans. The presence of nitrated CXCL8 was detected in bronchoalveolar lavage samples from patients with pneumonia, providing the first direct evidence of chemokine nitration in human pathophysiology.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lisa Verhallen, Jarkko J. J. Lackman, Rikke Wendt, Martin Gustavsson, Zhang Yang, Yoshiki Narimatsu, Daniel M. M. Sorensen, Kato Mac Lafferty, Mieke Gouwy, Pedro E. E. Marques, Gertrud M. M. Hjorto, Mette M. M. Rosenkilde, Paul Proost, Christoffer K. K. Goth
Summary: Chemokine ligands and receptors play a role in regulating leukocyte migration. This study examined the post-translational modifications of chemokine receptors and their impact on ligand binding and signaling. The results indicated that O-glycosylation and tyrosine sulfation affect the recognition and signaling of chemokines with the receptor CCR5. The enzymes GalNAc-T1 and GalNAc-T11 were identified as being involved in the O-glycosylation process of chemokine receptors.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Immunology
Karen Yu, Luna Dillemans, Mieke Gouwy, Helena Bessa, Mieke Metzemaekers, Erik Martens, Patrick Matthys, Xavier Bossuyt, Patrick Verschueren, Carine Wouters, Lien De Somer, Paul Proost
Summary: In this study, a fluorescent in vitro assay was improved to characterize endogenous PAD activity in complex samples. The results showed similar levels of PAD activity in synovial fluids of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) patients, while citrullination was limited in joints of patients with gout or Lyme's disease. Interestingly, a higher level of extracellular citrullination was only found in blood of anti-CCP-positive RA patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Luna Dillemans, Lien De Somer, Barbara Neerinckx, Paul Proost
Summary: Chemokines play a crucial role in initiating and perpetuating synovitis by promoting leukocytes migration into inflamed joints. The interaction between CXCR3 and CXCL9, CXCL10, and CXCL11 regulates the trafficking of various immune cells towards inflammatory niches. These chemokines are involved in autoinflammatory and autoimmune diseases, and their presence in bodily fluids of patients with inflammatory arthritis highlights their potential as therapeutic targets.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ana Carolina de Carvalho, Carlos Sato B. Dias, Lais D. Coimbra, Rebeca P. F. Rocha, Alexandre Borin, Marina A. Fontoura, Murilo Carvalho, Paul Proost, Mauricio L. Nogueira, Silvio R. Consonni, Renata Sesti-Costa, Rafael Elias Marques
Summary: Mayaro virus is an emerging arthropod-borne virus endemic in Latin America, causing arthritogenic febrile disease. In this study, a mouse model lacking type-I interferon receptor was used to explore the disease progression. The results showed that Mayaro virus infection in the hind paws of these mice led to visible inflammation, disseminated infection, and immune response activation. The histological analysis revealed edema in multiple tissues, which was associated with viral replication and the recruitment of immune cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Lowie Adyns, Paul Proost, Sofie Struyf
Summary: This review provides insights into the role of defensins in tumor immunity. Defensins, besides their antimicrobial activities, can directly lyse tumor cells, induce tumor cell apoptosis, attract and activate immune cells, and generate pro-inflammatory signals, contributing to the activation of the adaptive immune system and anti-tumor immunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Mieke Metzemaekers, Bert Malengier-Devlies, Mieke Gouwy, Lien De Somer, Fernando de Queiroz Cunha, Ghislain Opdenakker, Paul Proost
Summary: Neutrophils are powerful effector cells that play crucial roles in fighting pathogens and modulating immune responses. Recent evidence suggests that these cells are more versatile and heterogeneous than previously thought, and are involved in various diseases including cancer and autoimmune disorders. This review discusses the kinetics of neutrophils and their activation products, as well as their multifaceted functions in health and disease, focusing on studies using primary human cells.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Rheumatology
Bernard Grillet, Rafaela Vaz Sousa Pereira, Jo Van Damme, Ahmed Abu El-Asrar, Paul Proost, Ghislain Opdenakker
Summary: Proteolysis of the extracellular matrix is an irreversible post-translational modification in arthropathies like osteoarthritis and rheumatoid arthritis due to increased levels of matrix remodelling enzymes such as matrix metalloproteinases (MMPs). MMPs destroy proteoglycans, collagens, and other ECM molecules and also control joint remodelling indirectly through cell-surface receptors and cytokines. Understanding the regulation and activities of MMPs can help develop better diagnostics and therapies for joint diseases. MMPs play a significant role in irreversible joint remodelling in rheumatoid arthritis and osteoarthritis, making them important targets for precision medicine and diagnosis.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Seppe Cambier, Fabio Beretta, Noemie Portner, Mieke Metzemaekers, Ana Carolina de Carvalho, Erik Martens, Janne Kaes, Celine Aelbrecht, Cato Jacobs, Pierre Van Mol, Els Wauters, Philippe Meersseman, Greet Hermans, Rafael Elias Marques, Bart Vanaudenaerde, Robin Vos, Joost Wauters, Mieke Gouwy, Paul Proost
Summary: CXCL12, which is present in the lungs and circulation of COVID-19 patients, undergoes rapid proteolytic processing and degradation. The proteolysis is mainly mediated by neutrophil elastase in COVID-19 BAL fluids with high proteolytic activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Allergy
Toon Ieven, Lieve Coorevits, Martijn Vandebotermet, Sebastiaan Tuyls, Helene Vanneste, Lisa Santy, Dries Wets, Paul Proost, Glynis Frans, David Devolder, Christine Breynaert, Dominique M. A. Bullens, Rik Schrijvers
Summary: This study evaluated the tolerance of PEGylated lipid nanoparticle vaccine (BNT162b2) in patients with PEG and/or PS80 allergy and explored the mechanism of reactivity. The results showed that all PEG and/or PS80 allergic patients can safely receive SARS-CoV-2 vaccines.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Article
Medicine, Research & Experimental
Bruna M. Silva, Giovanni F. Gomes, Flavio P. Veras, Seppe Cambier, Gabriel V. L. Silva, Andreza U. Quadros, Diego B. Caetite, Daniele C. Nascimento, Camilla M. Silva, Juliana C. Silva, Samara Damasceno, Ayda H. Schneider, Fabio Beretta, Sabrina S. Batah, Icaro M. S. Castro, Isadora M. Paiva, Tamara Rodrigues, Ana Salina, Ronaldo Martins, Guilherme C. M. Cebinelli, Naira L. Bibo, Daniel M. Jorge, Helder I. Nakaya, Dario S. Zamboni, Luiz O. Leiria, Alexandre T. Fabro, Jose C. Alves-Filho, Eurico Arruda, Paulo Louzada-Junior, Rene D. Oliveira, Larissa D. Cunha, Pierre Van Mol, Lore Vanderbeke, Simon Feys, Els Wauters, Laura Brandolini, Andrea Aramini, Fernando Q. Cunha, Joerg Koehl, Marcello Allegretti, Diether Lambrechts, Joost Wauters, Paul Proost, Thiago M. Cunha
Summary: Activation of the C5a/C5aR1 pathway in COVID-19 patients can worsen the disease and lead to cytokine storm syndrome, organ dysfunction, and death. Inhibiting C5aR1 signaling can improve lung immunopathology, suggesting that C5aR1 antagonists may be useful for COVID-19 treatment.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Immunology
Seppe Cambier, Mieke Gouwy, Paul Proost
Summary: Chemokines play a crucial role in regulating leukocyte migration and activation in the immune system. CXCL8 is a potent chemokine that attracts neutrophils and is important in the response to infection and tissue injury. Its activity is dependent on interactions with specific chemokine receptors and glycosaminoglycans. Understanding the structure and regulation of CXCL8 is important for therapeutic development and managing inflammatory diseases and cancer.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Immunology
Luna Dillemans, Youri Bekhuis, Albrecht Betrains, Karen Yu, Maarten van Hemelen, Noemie Portner, Lien De Somer, Patrick Matthys, Jeroen Breckpot, Thomas Tousseyn, Marijke Peetermans, Paul Proost, Carine Wouters, Steven Vanderschueren
Summary: We report a fatal case of a 20-year-old woman with refractory adult-onset Still's disease accompanied by fulminant macrophage activation syndrome and atypical hemolytic uremic syndrome. This case highlights the importance of prompt genetic assessment of complement-encoding alleles, in addition to HLH-related genes, in patients with severe adult-onset Still's disease with recurrent macrophage activation syndrome and features of thrombotic microangiopathy.
CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Olav Larsen, Sara Schuermans, Anna Walser, Stavroula Louka, Ida Aaberg Lillethorup, Jon Vabeno, Katrine Qvortrup, Paul Proost, Mette M. Rosenkilde
Summary: This study investigates the signaling capacity of peptides related to inflammatory chemokines. The peptides showed weak potency but retained their signaling on CCR1, while none of the peptides generated a signal on CCR5. However, a tetrapeptide derived from CCL3 acted as a positive modulator on CCR5.