Article
Immunology
Hong-Wei Sun, Wen-Chao Wu, Hai-Tian Chen, Yi-Tuo Xu, Yan-Yan Yang, Jing Chen, Xing-Juan Yu, Zilian Wang, Ze-Yu Shuang, Limin Zheng
Summary: The study demonstrates that glutamine deprivation can enhance the expression of G-CSF and GM-CSF in breast cancer cells, leading to generation of immunosuppressive myeloid-derived suppressor cells (MDSCs) due to impaired HPC-maintaining capacity in the bone marrow.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Adria-Arnau Lindez, Walter Reith
Summary: Arginine plays a crucial role in regulating immune responses and its adequate supply is important for improving immune function. The availability, synthesis, and catabolism of arginine are interrelated aspects that affect immune cell biology profoundly. Disruption or perversion of arginine metabolism is implicated in various pathologies, from infectious diseases to autoimmunity and cancer.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Shang Xian Bo, Wang Yan Jie, Cai De Chao, Ma Sai, Wang Zhe, Zhu Ya Kun, Guo Hui Hui, Wang Chen, Ma Xiao, Hu Zhong Yao, Yu Hao Ran, Zhang Ji Sen, Cheng Wen Dan
Summary: The study demonstrated that compound 22o effectively inhibited the inflammatory response and catabolism of chondrocytes, reducing articular cartilage injury in a rat OA model induced by ACLT. The compound showed potential as a disease-modifying OA drug.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Noriyoshi Ogino, Hidekazu Takahashi, Kenjiro Nagaoka, Yuki Harada, Masayuki Kubo, Koichiro Miyagawa, Masashi Kusanaga, Shinji Oe, Yuichi Honma, Masaru Harada, Masamitsu Eitoku, Narufumi Suganuma, Keiki Ogino
Summary: The study found that the increase in arginase activity in the plasma of obese mice is positively correlated with blood glucose levels, along with an increase in exosomal arginase-1 levels. The liver of high-fat diet-fed mice showed a significant increase in arginase-1 expression, and exposure to high glucose increased the expression of arginase-1 in exosomes and total lysates of HepG2 cells.
Article
Biochemistry & Molecular Biology
Camila Alves Mota, Daniele Stefanie Sara Lopes Lera-Nonose, Aline Avila Brustolin, Giovanna Chiqueto Duarte, Maria Carolina Mota dos Santos, Maria Valdrinez Campana Lonardoni, Thais Gomes Verzignassi Silveira
Summary: This study investigated the expression pattern of HIF-1α gene during Leishmania infection in hamsters. The results showed that HIF-1α mRNA was down-regulated during chronic infection, but the inhibition was less pronounced in hamsters infected with L. lainsoni and L. naiffi. The expression of arginase gene was increased in animals infected with L. braziliensis, while IFN-γ and IL-10 gene expression were increased in animals infected with L. lainsoni and L. naiffi. Animals infected with L. lainsoni and L. naiffi showed better control of the disease.
Article
Immunology
Kelly L. Monaghan, Wen Zheng, Halima Akhter, Lei Wang, Amanda G. Ammer, Peng Li, Jian-Xin Lin, Gangqing Hu, Warren J. Leonard, Edwin C. K. Wan
Summary: In immune responses, monocytes have diverse functions such as pathogen clearance and tissue repair. However, abnormal control of monocyte activation can lead to chronic inflammation and tissue damage. This study reveals that GM-CSF-induced STAT5 tetramerization plays a critical role in determining monocyte fate and function. Monocytes require STAT5 tetramers to differentiate into moDCs, while the absence of STAT5 tetramers results in the differentiation into a distinct monocyte-derived macrophage population. In a colitis model, STAT5 tetramer-deficient monocytes worsen disease severity, and this is associated with overexpression of arginase I and reduced nitric oxide synthesis. Inhibition of arginase I and sustained supplementation of nitric oxide ameliorate the worsened colitis in STAT5 tetramer-deficient mice.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Yoshinori Kajiwara, Hiroshi Tazawa, Motohiko Yamada, Nobuhiko Kanaya, Takuro Fushimi, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Ryuichi Yoshida, Yuzo Umeda, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
Summary: GEM-resistant PDAC cells express high levels of PD-L1 and produce high levels of GM-CSF, leading to immunosuppressive tumor microenvironment and accumulation of MDSCs. OBP-702 can effectively inhibit the growth of GEM-resistant PDAC tumors and enhance the anti-tumor efficacy of PD-L1 blockade.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Zhengzheng Zhang, Zhiyan Yao, Zimeng Zhang, Ling Cui, Ling Zhang, Gang Qiu, Xiaotian Song, Shuxia Song
Summary: This study investigates the mechanism by which radiotherapy promotes the recruitment of M-MDSCs in the lung and increases the risk of lung metastasis in breast cancer. The findings show that radiotherapy increases the number of M-MDSCs in the lung, inhibits T cell function, and promotes MDSCs migration through the CXCL1/CXCR2 and CCL2/CCR2 signaling pathways. This study reveals a detrimental effect of radiotherapy in promoting immunosuppressive premetastatic niches formation in the lung.
CANCER CELL INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Shaimaa Maher, Lauren A. Smith, Celine A. El-Khoury, Haitham Kalil, Khalid Sossey-Alaoui, Mekki Bayachou
Summary: Nitric oxide (NO) is a small molecule that has a significant impact on various biological activities. It has been linked to cancer-related processes and has the potential to be used as an anti-cancer agent. In this study, NO-releasing materials were developed using modified sodium alginate hydrogel, which showed compatibility with cell growth. The release of NO from the hydrogel exhibited distinct kinetic features.
Article
Biochemistry & Molecular Biology
Tony Y. Momma, Javier I. Ottaviani
Summary: Under continuous L-arginine supply conditions, arginase does not affect NOS activity through substrate competition. The study also demonstrates that L-arginine pathways such as transporters and protein synthesis are more likely to affect NOS activity than arginase.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Article
Immunology
Arpa Aintablian, Sandra Strozniak, Marion Heuer, Manfred B. Lutz
Summary: Myeloid-derived suppressor cells (MDSC) are major regulators of immune responses, controlling T cells via their inducible nitric oxide synthase (iNOS) and arginase 1 (Arg1). IL-3, similar to GM-CSF, can generate monocytic MDSC (M-MDSC) with increased Arg1 expression and Arg1-dependent suppression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wasan Naser, Saeed Maymand, Daniel Dlugolenski, Faiza Basheer, Alister C. Ward
Summary: Cytokine-inducible SH2 domain-containing protein (CISH) is a member of the suppressor of cytokine signaling (SOCS) family and plays crucial roles in lymphoid cell development, function, and appetite regulation. This study revealed that CISH negatively regulates granulopoiesis, especially that mediated by GM-CSF. Knockout mice deficient in CISH exhibited increased levels of neutrophils in the blood, bone marrow, and spleen, suggesting the importance of CISH in myelopoiesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maricruz Mamani-Huanca, Sandra Marcia Muxel, Stephanie Maia Acuna, Lucile Maria Floeter-Winter, Coral Barbas, Angeles Lopez-Gonzalvez
Summary: The research analyzed the metabolic networks of macrophages infected by Leishmania parasites and found that the absence of parasite arginase affects host and parasite metabolism pathways, increases nitric oxide (NO) production, and enhances infectivity rate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Agnieszka Zablocka, Dominika Jakubczyk, Katarzyna Leszczynska, Katarzyna Pacyga-Prus, Jozefa Macala, Sabina Gorska
Summary: This study investigated the ability of Bifidobacterium species to induce iNOS-dependent NO synthesis in macrophages. The results showed that Bifidobacterium can regulate the expression of iNOS and produce NO by activating MAPK kinases. TLR2 and TLR4 receptors are involved in Bifidobacterium-induced macrophage activation and NO production. The study suggests that Bifidobacterium has a protective mechanism in the intestine, and its efficacy is strain-dependent.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2023)
Review
Physiology
Katharine L. Bunch, Ammar A. Abdelrahman, Ruth B. Caldwell, R. William Caldwell
Summary: Diabetic retinopathy (DR) and diabetic macular edema (DME) are complications of diabetes that can cause vision loss and reduced quality of life. Current treatments for advanced DR and DME are invasive, expensive, and can have adverse side-effects. Therefore, there is a need for more effective, affordable, and accessible therapies that can target early stage disease. Novel therapies under investigation include erythropoietin-derived peptides, inducers of antioxidant gene expression, activators of nitric oxide/cyclic GMP signaling pathways, and manipulation of arginase activity.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Immunology
Kirsten De Ridder, Hanne Locy, Elisa Piccioni, Miren Ibarra Zuazo, Robin Maximilian Awad, Stefaan Verhulst, Mathias Van Bulck, Yannick De Vlaeminck, Quentin Lecocq, Eva Reijmen, Wout De Mey, Lien De Beck, Thomas Ertveldt, Isabel Pintelon, Jean-Pierre Timmermans, David Escors, Marleen Keyaerts, Karine Breckpot, Cleo Goyvaerts
Summary: Immune checkpoint blockade of the PD-1 pathway has greatly improved the survival prognosis for advanced non-small cell lung cancer (NSCLC). However, many PD-L1(+) NSCLC patients are resistant to anti-PD-L1 therapy. This study found that PD-L1(+) tumor-infiltrating myeloid cells play a crucial role in the failure of therapy. Anti-PD-L1 therapy induced a monocyte-specific production and response to TNF-alpha, accompanied by increased expression of CD80, VISTA, LAG-3, SIRP-alpha, and TIM-3. However, co-blockade of PD-L1 and TNF-alpha did not reduce tumor growth.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biology
Luisa Chocarro, Hugo Arasanz, Leticia Fernandez-Rubio, Ester Blanco, Miriam Echaide, Ana Bocanegra, Lucia Teijeira, Maider Garnica, Idoia Morilla, Maite Martinez-Aguillo, Sergio Pineiro-Hermida, Pablo Ramos, Juan Jose Lasarte, Ruth Vera, Grazyna Kochan, David Escors
Summary: Adoptive cell therapy with genetically modified T lymphocytes that express chimeric antigen receptors (CAR-T) has shown promising outcomes in treating hematological malignancies, but its efficacy in solid tumors is still unsatisfactory due to the immunosuppressive tumor microenvironment. Developing personalized CAR-T cells and identifying therapeutic targets are necessary to improve the treatment of solid tumors.
Article
Oncology
Hugo Arasanz, Ana Isabel Bocanegra, Idoia Morilla, Joaquin Fernandez-Irigoyen, Maite Martinez-Aguillo, Lucia Teijeira, Maider Garnica, Ester Blanco, Luisa Chocarro, Karina Ausin, Miren Zuazo, Gonzalo Fernandez-Hinojal, Miriam Echaide, Leticia Fernandez-Rubio, Sergio Pineiro-Hermida, Pablo Ramos, Laura Mezquita, David Escors, Ruth Vera, Grazyna Kochan
Summary: This study investigated the role of baseline circulating low-density neutrophils (LDN) in NSCLC patients, identifying LDN as a predictive biomarker for immunotherapy resistance. Combining immunotherapy with chemotherapy can reduce LDN levels, overcome resistance, and suggest potential drug combinations for improved outcomes.
Review
Cell Biology
Luisa Chocarro, Ana Bocanegra, Ester Blanco, Leticia Fernandez-Rubio, Hugo Arasanz, Miriam Echaide, Maider Garnica, Pablo Ramos, Sergio Pineiro-Hermida, Ruth Vera, David Escors, Grazyna Kochan
Summary: Immune checkpoint inhibitors (ICIs) have revolutionized oncology practice, with Lymphocyte-Activation Gene 3 (LAG-3) being a key next-generation immune checkpoint molecule. Clinical trials have shown positive results for LAG-3 targeting molecules. The recent FDA approval of a dual anti-PD-1 and anti-LAG-3 treatment has significantly improved progression-free survival.
Review
Biochemistry & Molecular Biology
Ester Blanco, Luisa Chocarro, Leticia Fernandez-Rubio, Ana Bocanegra, Hugo Arasanz, Miriam Echaide, Maider Garnica, Sergio Pineiro-Hermida, Grazyna Kochan, David Escors
Summary: Immunotherapies based on immune checkpoint blockade have shown promising clinical outcomes but lack efficacy in most cancer patients. Intratumor delivery of monoclonal antibodies (mAbs) has emerged as a potential solution to reduce adverse events and improve treatment efficacy. Gene therapy vectors expressing mAbs inside tumors offer an attractive approach for local intratumor delivery. This expanding research subject will likely play a key role in future oncology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Vincent Vinh-Hung, Olena Gorobets, Nele Adriaenssens, Hilde Van Parijs, Guy Storme, Dirk Verellen, Nam P. Nguyen, Nicolas Magne, Mark De Ridder
Summary: This study observed the follow-up of 123 women with stage I-II breast cancer who underwent adjuvant radiotherapy for over 10 years. The study found that there was higher mortality in 2020, with an increase in lung-heart toxicity and a decline in lung-heart function.
Review
Biochemistry & Molecular Biology
Hugo Arasanz, Luisa Chocarro, Leticia Fernandez-Rubio, Ester Blanco, Ana Bocanegra, Miriam Echaide, Ibone Labiano, Ana Elsa Huerta, Maria Alsina, Ruth Vera, David Escors, Grazyna Kochan
Summary: Bispecific antibodies hold promise as a therapy for cancer, demonstrating the ability to simultaneously inhibit multiple proteins involved in cancer progression. In lung cancer treatment, their development has been particularly intense due to extensive knowledge of underlying molecular pathways, especially in oncogene-driven tumors. This review provides an overview of the current landscape of bispecific antibodies in lung cancer treatment and discusses potential future expansion of their role.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Inigo Les, Mireia Martinez, Ines Perez-Francisco, Maria Cabero, Lucia Teijeira, Virginia Arrazubi, Nuria Torrego, Ana Campillo-Calatayud, Inaki Elejalde, Grazyna Kochan, David Escors
Summary: Immune-checkpoint inhibitors (ICIs) are widely used in cancer treatment, but they can cause immune-related adverse events (irAEs) in a significant number of patients. Predicting irAEs has become important for managing patients on ICIs. This review discusses biomarkers that have shown potential for predicting irAEs, including those already available for clinical use and those under investigation. Although these biomarkers have not been validated in prospective studies, there is growing evidence supporting their use for predicting and characterizing irAEs, which depend on factors such as the type of cancer, ICI agent, and affected organ. Further research is needed to understand the mechanisms of irAEs and to assess the predictive capacity of different biomarkers.
Review
Geriatrics & Gerontology
Mariam Hebishy, Cabirou Mounchili Shintouo, Ines Dufait, Florence Debacq-Chainiaux, Ivan Bautmans, Rose Njemini
Summary: Cellular senescence is a permanent arrest of cell growth and has important roles in tumor suppression, wound healing, tissue regeneration, and prevention of tissue fibrosis. The relationship between Heat Shock Proteins (HSP) and cellular senescence in humans lacks comprehensive investigation. This systematic review summarizes the literature on the prospective role of HSP in the development of cellular senescence in humans.
ARCHIVES OF GERONTOLOGY AND GERIATRICS
(2023)
Article
Biochemistry & Molecular Biology
Ana Bocanegra, Gonzalo Fernandez-Hinojal, Daniel Ajona, Ester Blanco, Miren Zuazo, Maider Garnica, Luisa Chocarro, Elvira Alfaro-Arnedo, Sergio Pineiro-Hermida, Pilar Morente, Leticia Fernandez, Ana Remirez, Miriam Echaide, Maite Martinez-Aguillo, Idoia Morilla, Beatriz Tavira, Alejandra Roncero, Carolina Gotera, Alfonso Ventura, Nerea Recalde, Jose G. Pichel, Juan Jose Lasarte, Luis Montuenga, Ruth Vera, Ruben Pio, David Escors, Grazyna Kochan
Summary: Recent studies show that baseline functional immunity is crucial for the success of immune checkpoint blockade therapies. In this study, high-dimensional systemic immune profiling was performed on non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders had a higher diversity of myeloid phenotypes in their peripheral blood. A diversity index was defined as a potential biomarker of response. Fractalkine (FKN), a chemokine linked to immune chemotaxis and adhesion, was identified as a biomarker of response and correlated with myeloid cell diversity. FKN inhibited lung adenocarcinoma growth in both human and mouse models through the involvement of systemic effector NK cells and increased tumor immune infiltration. FKN also sensitized mouse lung cancer models resistant to anti-PD-1 treatment to immunotherapy, indicating its potential therapeutic use in combination with immunotherapy.
Article
Oncology
Benedikt Engels, Antonino De Paoli, Elena Delmastro, Fernando Munoz, Stefano Vagge, Darius Norkus, Hendrik Everaert, Gianna Tabaro, Elisabetta Gariboldi, Umberto Ricardi, Eugenio Borsatti, Pietro Gabriele, Roberto Innocente, Elisa Palazzari, Emilie Dubaere, Marc-Andre Mahe, Sven Van Laere, Thierry Gevaert, Mark De Ridder
Summary: This study compared the efficacy of standard chemoradiotherapy and radiotherapy with a simultaneous integrated boost (SIB) for rectal cancer. The results showed no significant difference between the two treatments in terms of primary and secondary endpoints. SIB can be considered as a treatment option for T3-4 rectal cancer patients who are unable to tolerate chemotherapy.
Article
Endocrinology & Metabolism
Marta Redondo-Munoz, Francisco Javier Rodriguez-Baena, Paula Aldaz, Adria Caballe-Mestres, Veronica Moncho-Amor, Maddalen Otaegi-Ugartemendia, Estefania Carrasco-Garcia, Ana Olias-Arjona, Irene Lasheras-Otero, Eva Santamaria, Ana Bocanegra, Luisa Chocarro, Abby Grier, M. Monika Dzieciatkowska, Claudia Bigas, Josefina Martin, Uxue Urdiroz-Urricelqui, Florencio Marzo, Enrique Santamaria, Grazyna Kochan, David Escors, Ignacio Marcos Larrayoz, Holger Heyn, Angelo D'Alessandro, Camille Stephan-Otto Attolini, Ander Matheu, Claudia Wellbrock, Salvador Aznar Benitah, Berta Sanchez-Laorden, Imanol Arozarena
Summary: In this study, the anti-anginal drug ranolazine is found to sensitize BRAF inhibitor-resistant melanoma to targeted therapy and immunotherapy by rewiring fatty acid oxidation and the methionine salvage pathway. Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring.
Article
Engineering, Electrical & Electronic
Amir L. Rifi, Ines Dufait, Chaimae El Aisati, Mark De Ridder, Kurt Barbe
Summary: Radiomic features are important for predicting tumor grade and treatment response, however their lack of interpretability hinders clinical application. This study proposes an innovative approach to correlate biological meaning to specific radiomic features using in vivo experiments. The results show that the radiomic features allow for distinguishable differences between tumor models and display high repeatability, indicating the feasibility of this approach in routine clinical practice.
IEEE TRANSACTIONS ON INSTRUMENTATION AND MEASUREMENT
(2023)
Article
Biology
P. Janssen, L. De Pauw, M. Mambretti, O. Lara, J. Walckiers, L. Mackens, I. Rooman, B. Guillaume, M. De Ridder, G. Ates, A. Massie
Summary: TBI followed by BMT had long-term impact on weight and locomotion but minimal effect on anxiety and depressive behavior. Impaired neurogenesis and cortical microglia activation were observed after TBI/BMT, and increased BBB permeability potentially contributed to the memory deficit.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)