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Immune checkpoint inhibitors:breakthroughs in cancer treatment

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Cancer biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of immunology and Inflammation School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University department of biology School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade(ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies(mAbs) are currently available as immune checkpoint inhibitors(ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4) and programmed cell death protein 1(PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response.Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1(anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains(TIGIT), mucin domain containing-3(TIM-3), lymphocyte activation gene-3(LAG-3), V-domain immunoglobulin suppressor of T cell activation(VISTA), B and T lymphocyte attenuator(BTLA), and signal-regulatory protein α(SIRPα). Functional m Abs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： CTLA-4 ICIs Immunotherapy PD-1 cancer

Identification of gene classifier and modules associated with SARS-CoV-2 ARI in nasal swab

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Genes & Diseases 2024年第1期11卷 38-41页

作者： Pandikannan Krishnamoorthy Athira S.Raj Himanshu Kumar department of Biological Sciences Laboratory of Immunology and Infectious Disease BiologyIndian Institute of Science Education and Research(llSER)BhopalBhopalMP 462066India Laboratory of Host Defense WPl ImmunologyFrontier ResearchCentreOsakaUniversityOsaka 5650871Japan

During a sudden viral pandemic,where the pathogenesis and nature of the infection are unclear,early and accurate identification of the patients infected with the pandemiccausing pathogen is crucial to prevent excess mortality.During the coronavirus disease 2019(COvID-19)pandemic,early diagnosis of severe acute respiratory syndrome virus-2(SARS-CoV-2)is limited by the incidence of the symptoms that are shared with acute respiratory illnesses(ARl)caused by other pathogens.

关键词： acute diagnosis respiratory

Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system

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Signal Transduction and Targeted Therapy 2024年第1期9卷 12-13页

作者： Marianne Boes Pascal Falter-Braun Center for Translational immunology and department of Pediatric immunology University Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands Institute of Network biology(INET) Molecular Targets and Therapeutics Center(MTTC)Helmholtz MunichNeuherbergGermany Microbe-Host Interactions Faculty of BiologyLudwig-Maximilians-Universität MünchenPlanegg-MartinsriedGermany

In a recent Cell publication,Cheong et al.uncover how COVID-19 causes IL-6 induced epigenetic reprogramming of human immune stem cells,which causes lasting alterations in the composition and response characteristics of circulating immune cells.1 The study provides important insights into the mechanisms by which SARSCoV-2 infections impact the human immune system and is an important hook into unraveling the mechanisms of post-acute sequelae of COVID-19(PASC)commonly referred to as longCOVID.

关键词： system COV programming

Progress in gut microbiota-host interaction

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Science China(Life Sciences) 2024年第5期67卷 851-853页

作者： Changtao Jiang department of immunology School of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking UniversityBeijing 100191China

Recently,the gut microbiota has been recognized as a novel endocrine organ in the human body.It produces various bioactive metabolites and participates in metabolic processes.In addition,the gut microbiota is involved in the metabolism of drugs and natural components,which in turn influences the effects of various oral medications.

关键词： metabolism drugs processes

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Role of ACLY in the development of gastric cancer under hyperglycemic conditions

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Quantitative biology 2024年第1期12卷 100-116页

作者： Keran Sun Jingyuan Ning Keqi Jia Xiaoqing Fan Hongru Li Jize Ma Meiqi Meng Cuiqing Ma Lin Wei department of immunology Immunology Department of Hebei Medical UniversityShijiazhuangChina department of Pathology Pathology Department of the Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

To investigate the impact of hyperglycemia on the prognosis of patients with gastric cancer and identify key molecules associated with high glucose levels in gastric cancer development,RNA sequencing data and clinical features of gastric cancer patients were obtained from The Cancer Genome Atlas(TCGA)database.High glucose-related genes strongly associated with gastric cancer were identified using weighted gene co-expression network and differential analyses.A gastric cancer prognosis signature was constructed based on these genes and patients were categorized into high-and low-risk groups.The immune statuses of the two patient groups were compared.ATP citrate lyase(ACLY),a gene significantly related to the prognosis,was found to be upregulated upon high-glucose stimulation.Immunohistochemistry and molecular analyses confirmed high ACLY expression in gastric cancer tissues and cells.Gene Set Enrichment Analysis(GSEA)revealed the involvement of ACLY in cell cycle and DNA replication processes.Inhibition of ACLY affected the proliferation and migration of gastric cancer cells induced by high glucose levels.These findings suggest that ACLY,as a high glucose-related gene,plays a critical role in gastric cancer progression.

关键词： ACLY gastric cancer high glucose immune microenvironment

Autophagy in neural stem cells and glia for brain health and diseases

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Neural Regeneration Research 2024年第4期19卷 729-736页

作者： Aarti Nagayach Chenran Wang department of Cancer biology University of Cincinnati College of Medicine

Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured tissues.Thus,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.

关键词： astrocyte autophagy glia microglia neural stem cells neurodegenerative diseases neurodevelopmental disorders oligodendrocyte

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim department of immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea department of immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B cells.Adoptive transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B cells.In summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

The anti-neoplastic effects of metformin modulate the acquired phenotype of fbroblast cells in the breast cancer-normal fbroblast co-culture system

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Oncology Research 2024年第3期32卷 477-487页

作者： SAMANEH MOSTAFAVI ZUHAIR MOHAMMAD HASSAN department of immunology Faculty of Medical SciencesTarbiat Modares UniversityTehranIran

Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation,growth,and therapy resitance.The hallmarks of cancer fibroblast interactions,consisting of caveolin 1(Cav1)and mono-carboxylate ransporter 4(MCT4)(metabolic coupling markers),along with IL-6,TGFB,and lactate secretion,are considered robust biomarkers predicting recurrence and metastasis.In order to promote a novel phenotype in normal fibroblasts,we predicted that breast cancer cells could be able to cause loss of Cavl and increase of MCT4,as well as elevate IL 6 and TGF in nearby nomal fibroblasts.We created a co culture model using breast cancer(4T1)and normal fibroblast(NIH3T3)cell lines cultured under specific experimental conditions in order to directly test our theory.Moreover,we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cavl and gain of MCT4 in adjacent fibroblasts and increase lactate secretion.These results were validated using the monoculture of each group separately as a control.In this system,we show that me tformin inhibits IL-6 and TGFB secretion and re expresses Cavl in both cells.However,MCT4 and lactate stayed high after treatment with metformin.In conclusion,our work shows that co-culture with breast cancer cells may cause signifcant alterations in the phenotype and secretion of normal fibroblasts.Metformin,however,may change this state and affect fibroblasts'acquired phenotypes.Moreover,mitochondrial inhibition by metformin after 8 days of treatment,signi ficantly hinders tumor growth in mouse model of breast cancer.

关键词： Caveolin 1 Lactic acid Metformin NIH 3T3 cells Neoplasms

Metabolic reprogramming of the inflammatory response in the nervous system:the crossover between inflammation and metabolism

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Neural Regeneration Research 2024年第10期19卷 2189-2201页

作者： Jesus Amo-Aparicio Charles A.Dinarello Ruben Lopez-Vales department of Medicine University of ColoradoAuroraCOUSA Institute of Neurosciences and Department Cell BiologyPhysiology and ImmunologyUniversitat Autònoma de BarcelonaBellaterraSpain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos ⅢSpain

Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

关键词： central nervous system fatty acid oxidation glycolysis inflammation macrophage metabolism microglia neurodegeneration oxidative phosphorylation

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