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1.
Front Immunol ; 15: 1316778, 2024.
Article in English | MEDLINE | ID: mdl-38482008

ABSTRACT

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Lymphocytes are the primary executors of the immune system and play essential roles in tumorigenesis and development. We investigated the dynamic changes in peripheral blood lymphocyte subsets to predict the efficacy of chemotherapy or combination immunotherapy in NSCLC. Methods: This retrospective study collected data from 81 patients with NSCLC who received treatments at the First Affiliated Hospital of Zhengzhou University from May 2021 to May 2023. Patients were divided into response and non-response groups, chemotherapy and combination immunotherapy groups, and first-line and multiline groups. We analyzed the absolute counts of each lymphocyte subset in the peripheral blood at baseline and after each treatment cycle. Within-group and between-group differences were analyzed using paired Wilcoxon signed-rank and Mann-Whitney U tests, respectively. The ability of lymphocyte subsets to predict treatment efficacy was analyzed using receiver operating characteristic curve and logistic regression. Results: The absolute counts of lymphocyte subsets in the response group significantly increased after the first cycle of chemotherapy or combination immunotherapy, whereas those in the non-response group showed persistent decreases. Ratios of lymphocyte subsets after the first treatment cycle to those at baseline were able to predict treatment efficacy early. Combination immunotherapy could increase lymphocyte counts compared to chemotherapy alone. In addition, patients with NSCLC receiving chemotherapy or combination immunotherapy for the first time mainly presented with elevated lymphocyte levels, whereas multiline patients showed continuous reductions. Conclusion: Dynamic surveillance of lymphocyte subsets could reflect a more actual immune status and predict efficacy early. Combination immunotherapy protected lymphocyte levels from rapid decrease and patients undergoing multiline treatments were more prone to lymphopenia than those receiving first-line treatment. This study provides a reference for the early prediction of the efficacy of clinical tumor treatment for timely combination of immunotherapy or the improvement of immune status.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/pathology , Retrospective Studies , Lymphocyte Count , Lymphocyte Subsets/pathology , Immunotherapy/adverse effects
2.
J Immunother Cancer ; 11(11)2023 11 28.
Article in English | MEDLINE | ID: mdl-38016719

ABSTRACT

BACKGROUNDS: G-protein-coupled receptor 84 (GPR84) marks a subset of myeloid-derived suppressor cells (MDSCs) with stronger immunosuppression in the tumor microenvironment. Yet, how GPR84 endowed the stronger inhibition of MDSCs to CD8+ T cells function is not well established. In this study, we aimed to identify the underlying mechanism behind the immunosuppression of CD8+ T cells by GPR84+ MDSCs. METHODS: The role and underlying mechanism that MDSCs or exosomes (Exo) regulates the function of CD8+ T cells were investigated using immunofluorescence, fluorescence activating cell sorter (FACS), quantitative real-time PCR, western blot, ELISA, Confocal, RNA-sequencing (RNA-seq), etc. In vivo efficacy and mechanistic studies were conducted with wild type, GPR84 and p53 knockout C57/BL6 mice. RESULTS: Here, we showed that the transfer of GPR84 from MDSCs to CD8+ T cells via the Exo attenuated the antitumor response. This inhibitory effect was also observed in GPR84-overexpressed CD8+ T cells, whereas depleting GPR84 elevated CD8+ T cells proliferation and function in vitro and in vivo. RNA-seq analysis of CD8+ T cells demonstrated the activation of the p53 signaling pathway in CD8+ T cells treated with GPR84+ MDSCs culture medium. While knockout p53 did not induce senescence in CD8+ T cells treated with GPR84+ MDSCs. The per cent of GPR84+ CD8+ T cells work as a negative indicator for patients' prognosis and response to chemotherapy. CONCLUSIONS: These data demonstrated that the transfer of GPR84 from MDSCs to CD8+ T cells induces T-cell senescence via the p53 signaling pathway, which could explain the strong immunosuppression of GPR84 endowed to MDSCs.


Subject(s)
Myeloid-Derived Suppressor Cells , Animals , Humans , Mice , CD8-Positive T-Lymphocytes , Immunosuppression Therapy , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , T-Cell Exhaustion , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
4.
Nat Immunol ; 24(12): 2042-2052, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37919525

ABSTRACT

Tumor-derived factors are thought to regulate thrombocytosis and erythrocytopenia in individuals with cancer; however, such factors have not yet been identified. Here we show that tumor cell-released kynurenine (Kyn) biases megakaryocytic-erythroid progenitor cell (MEP) differentiation into megakaryocytes in individuals with cancer by activating the aryl hydrocarbon receptor-Runt-related transcription factor 1 (AhR-RUNX1) axis. During tumor growth, large amounts of Kyn from tumor cells are released into the periphery, where they are taken up by MEPs via the transporter SLC7A8. In the cytosol, Kyn binds to and activates AhR, leading to its translocation into the nucleus where AhR transactivates RUNX1, thus regulating MEP differentiation into megakaryocytes. In addition, activated AhR upregulates SLC7A8 in MEPs to induce positive feedback. Importantly, Kyn-AhR-RUNX1-regulated MEP differentiation was demonstrated in both humanized mice and individuals with cancer, providing potential strategies for the prevention of thrombocytosis and erythrocytopenia.


Subject(s)
Neoplasms , Thrombocytosis , Animals , Mice , Kynurenine/metabolism , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Megakaryocytes/metabolism , Core Binding Factor Alpha 2 Subunit/genetics , Core Binding Factor Alpha 2 Subunit/metabolism , Erythroid Precursor Cells/metabolism , Cell Differentiation/physiology , Neoplasms/metabolism , Thrombocytosis/metabolism , Bias
5.
Materials (Basel) ; 16(9)2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37176342

ABSTRACT

Bamboo fiber is a natural and environmentally friendly material made from cheap and widely available resources and is commonly selected as the reinforcement material for steel-wire-mesh BFRPbar concrete beams. In this work, the effects of various fiber lengths and fiber volume rates on the shear properties of bamboo-fiber-reinforced steel-wire-mesh basalt fiber composite reinforcement concrete beams were studied through a combination of shear tests and numerical simulations. The findings demonstrate that the addition of bamboo fiber improves the cracking performance of the beam. The improvement effect of 45 mm bamboo fiber mixed with a 1% volume rate was the most obvious at about 31%. Additionally, the test beam's total stiffness was increased, and the deflection was decreased. However, the use of bamboo fiber was found to decrease the concrete's compressive strength, lowering the final shear capacity for the majority of beams. A method for estimating the shear capacity of the bamboo-fiber-reinforced steel-wire-mesh BFRPbar concrete beams is provided and lays the foundation for engineering practice, in accordance with the impact of bamboo fiber and steel wire mesh on beams that suffer shear breaks.

6.
Rev. bras. med. esporte ; 29: e2023_0045, 2023. tab, graf
Article in English | LILACS-Express | ID: biblio-1431631

ABSTRACT

ABSTRACT Introduction: Volleyball demands from athletes in continuous training a strong engagement and the use of sport endurance techniques, and their relaxation after training is indispensable. Objective: This paper investigates whether relaxation training after volleyball is beneficial in the competitive levels of volleyball players. Methods: 60 volleyball players aged 20-23 years were selected as participants in the experiment. They received relaxation training for 8 weeks, and heart rate changes were recorded before and after relaxation. Results: The heart rate of athletes in a resting state before training changed from 79.93 in the first week to 81.07 in the eighth week; after volleyball practice, the heart rate of athletes before relaxation varied from 136.13 to 140.73 from the first week to the eighth week; after the introduction of relaxation training, the heart rate of athletes was 84.71, and the minimum heart rate recorded was 80.74. It can be seen that relaxation training allows athletes to recover quickly to a normal state and achieve the goal of relaxation. Conclusion: Adding a relaxation training program to relieve fatigue after volleyball showed a useful for improving the performance of volleyball players. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.


RESUMO Introdução: O voleibol exige dos atletas em formação contínua um forte engajamento e o uso de técnicas de resistência ao esporte, sendo indispensável o seu relaxamento após o treino. Objetivo: Este artigo investiga se o treinamento de relaxamento após o voleibol é benéfico nos níveis competitivos dos jogadores de voleibol. Métodos: 60 jogadores de voleibol de 20 a 23 anos de idade foram selecionados como participantes do experimento. Eles receberam treinamento de relaxamento por 8 semanas, registrando-se as alterações do ritmo cardíaco antes e depois do relaxamento. Resultados: O ritmo cardíaco dos atletas em estado de repouso antes do treinamento mudou de 79,93 na primeira semana para 81,07 na oitava semana; após a prática do voleibol, o ritmo cardíaco dos atletas antes do relaxamento variou de 136,13 a 140,73 da primeira semana para a oitava semana; após a introdução do treinamento de relaxamento, a frequência cardíaca dos atletas foi de 84,71, sendo a frequência cardíaca mínima registrada de 80,74. Pode-se observar que o treinamento de relaxamento permite aos atletas se recuperarem rapidamente para um estado normal e alcançarem o objetivo de relaxamento. Conclusão: Adicionar o programa de treinamento de relaxamento para aliviar a fadiga após o vôlei evidenciou-se útil para melhorar o desempenho dos jogadores de vôlei. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción: El voleibol exige de los deportistas en entrenamiento continuo un fuerte compromiso y la utilización de técnicas de resistencia deportiva, siendo imprescindible su relajación después del entrenamiento. Objetivo: Este trabajo investiga si el entrenamiento de relajación después del voleibol es beneficioso en los niveles competitivos de los jugadores de voleibol. Métodos: 60 jugadoras de voleibol de entre 20 y 23 años fueron seleccionadas como participantes en el experimento. Recibieron entrenamiento de relajación durante 8 semanas y se registraron los cambios en la frecuencia cardiaca antes y después de la relajación. Resultados: La frecuencia cardíaca de los deportistas en estado de reposo antes del entrenamiento varió de 79,93 en la primera semana a 81,07 en la octava semana; tras la práctica del voleibol, la frecuencia cardíaca de los deportistas antes de la relajación varió de 136,13 a 140,73 desde la primera semana hasta la octava semana; tras la introducción del entrenamiento de relajación, la frecuencia cardíaca de los deportistas fue de 84,71, y la frecuencia cardíaca mínima registrada fue de 80,74. Se puede observar que el entrenamiento de relajación permite a los atletas recuperarse rápidamente a un estado normal y alcanzar el objetivo de la relajación. Conclusión: Añadir el programa de entrenamiento de relajación para aliviar la fatiga después del voleibol se mostró útil para mejorar el rendimiento de los jugadores de voleibol. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

7.
Adv Mater ; : e2301772, 2023 May 06.
Article in English | MEDLINE | ID: mdl-37148503

ABSTRACT

The practical application of metalloid black phosphorus (BP) based anodes for potassium ion batteries is mainly impeded by its instability in air and irreversible/sluggish potassium storage behaviors. Herein, a 2D composite is purposefully conceptualized, where ultrathin BP nanodisks with Fe3 O4 nanoclusters are hybridized with Lewis acid iron (V)-oxo complex (FC) nanosheets (denoted as BP@Fe3 O4 -NCs@FC). The introduced electron coordinate bridge between FC and BP, and hydrophobic surface of FC synergistically assure that BP@Fe3 O4 -NCs@FC is ultrastable in humid air. With the purposeful structural and componential design, the resultant BP@Fe3 O4 -NCs@FC anode is endowed with appealing electrochemical performance in terms of reversible capacity, rate behavior, and long-duration cycling stability in both half and full cells. Furthermore, the underlying formation and potassium-storage mechanisms of BP@Fe3 O4 -NCs@FC are tentatively proposed. The in-depth insights here will provide a crucial understanding in rational exploration of advanced anodes for next-generation PIBs.

8.
Signal Transduct Target Ther ; 8(1): 164, 2023 04 28.
Article in English | MEDLINE | ID: mdl-37105980

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) were found to gradually accumulate in the orthotopic esophageal cancer mouse model during tumor progression. Although the roles of MDSCs in promoting tumor growth and inhibiting immune response have been extensively explored, currently, there are still no effective means for targeting MDSCs clinically. The deficiency of specific markers of MDSCs was responsible for the limited strategy to eliminating in clinic. This study identified that GPR84 was exclusively overexpressed on MDSCs. It was further found that GPR84 was prominently expressed on MDSCs in clinical samples and tumor mouse models, which drives the immunosuppression on CD8+T cells by inhibiting PD-L1 degradation in lysosomes. Furthermore, G-CSF and GM-CSF were found to induce GPR84 expression through the STAT3/C/EBPß signaling pathway. In addition, GPR84+MDSCs and PD-L1+MDSCs were highly accumulated in anti-PD-1 therapy-resistant patients with esophageal cancer, and high GPR84 signature risk was verified as a negative factor for the overall survival of patients with anti-PD-1 treatment. Finally, GPR84 antagonism combined with an anti-PD-1 antibody enhanced the antitumor responses. Therefore, targeting GPR84 enhanced anti-PD-1 efficacy in esophageal cancer and other malignant tumors. This combination therapy has the potential for tumor therapy in clinics.


Subject(s)
Esophageal Neoplasms , Myeloid-Derived Suppressor Cells , Animals , Mice , B7-H1 Antigen , Immunotherapy , Disease Models, Animal , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism
9.
Angew Chem Int Ed Engl ; 62(19): e202300599, 2023 May 02.
Article in English | MEDLINE | ID: mdl-36826470

ABSTRACT

Antimony (Sb)-based anodes are attractive candidates in potassium-ion batteries (PIBs) due to their superior capacities and rational potassium inserting voltages. However, the sluggish kinetics and poor interface compatibility severely hinder practical application. Herein, Bi0.67 Sb1.33 S3 nanospheres embedded into in situ formed poly(3,4-ethylenedioxythiophene) crosslinked with polythioctic acid (PET@PTA) (Bi0.67 Sb1.33 S3 /PET@PTA) were elaborately conceptualized with hydrogen bonds exchangeable binding (HBEB) sites. Bi0.67 Sb1.33 S3 /PET@PTA exhibits notable self-healing ability and wider temperature adaptability. Bi0.67 Sb1.33 S3 /PET@PTA displays an impressive capacity of 819 mAh g-1 at 0.05 A g-1 , prominent cycle ability with a 73 % capacity conservation after 500 cycles at 2 A g-1 , and high capacity retention of 66 % and 84 % at -40 and 70 °C to that case at room temperature, respectively, for potassium storage. This work provides a new perspective for HBEB sites in maximizing the desirable K+ storage performance.

10.
J Immunol ; 209(6): 1039-1047, 2022 09 15.
Article in English | MEDLINE | ID: mdl-35970555

ABSTRACT

Melanoma-associated Ag (MAGE)-C2, an immunogenic cancer germline (testis) Ag, is highly expressed by various tumor cells, thymic medullary epithelial cells, and germ cells. In this study, we aimed to explore the immunologic properties of MAGE-C2-specific CD8+ T cells and the relationship of its TCR ß-chain V region (TCR vß) subfamily distribution to prognosis of patients with esophageal cancer. PBMCs and tumor-infiltrating lymphocytes expanded by CD3/CD28 Dynabeads and MAGE-C2 peptides in vitro resulted in the induction of lysosome-associated membrane protein-1 (LAMP-1 or CD107a) on the cell surface and the production of IFN-γ by MAGE-C2-specific CD8+ T cells. We found differential TCR vß subfamily distribution among flow-sorted CD107a+IFN-γ+ and CD107a-IFN-γ- CD8+ T cells. The proportion of CD107a+ and/or IFN-γ+ tetramer+ CD8+ T cells was lower in patients with lymph node metastasis, late tumor stage, and poorly differentiated state (p < 0.05). T-box transcription factor was positively correlated with CD107a and IFN-γ. Kaplan-Meier analysis showed that patients whose MAGE-C2-specific CD8+ T cells expressed high CD107a and/or IFN-γ had a longer survival time when compared with patients whose MAGE-C2-specific CD8+ T cells expressed low levels of CD107a and/or IFN-γ. Moreover, analysis of TCR vß subfamily distribution revealed that a higher frequency of TCR vß16 in MAGE-C2-specific CD8+ T cells was positively correlated with a better prognosis. These results suggest that the presence of functional MAGE-C2-specific CD8+ T cells had an independent prognostic impact on the survival of patients with esophageal cancer.


Subject(s)
Esophageal Neoplasms , Melanoma , Antigens, Neoplasm , CD28 Antigens/metabolism , CD8-Positive T-Lymphocytes , Humans , Neoplasm Proteins , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell, alpha-beta , Transcription Factors/metabolism
11.
Cell Biosci ; 12(1): 60, 2022 May 14.
Article in English | MEDLINE | ID: mdl-35568876

ABSTRACT

BACKGROUND: Epitranscriptomics studies have contributed greatly to the development of research on human cancers. In recent years, N6-methyladenosine (m6A), an RNA modification on the N-6 position of adenosine, has been found to play a potential role in epigenetic regulation. Therefore, we aimed to evaluate the regulation of cancer progression properties by m6A. RESULTS: We found that m6A demethylase fat mass and obesity-associated protein (FTO) was highly expressed in esophageal cancer (EC) stem-like cells, and that its level was also substantially increased in EC tissues, which was closely correlated with a poor prognosis in EC patients. FTO knockdown significantly inhibited the proliferation, invasion, stemness, and tumorigenicity of EC cells, whereas FTO overexpression promoted these characteristics. Furthermore, integrated transcriptome and meRIP-seq analyses revealed that HSD17B11 may be a target gene regulated by FTO. Moreover, FTO promoted the formation of lipid droplets in EC cells by enhancing HSD17B11 expression. Furthermore, depleting YTHDF1 increased the protein level of HSD17B11. CONCLUSIONS: These data indicate that FTO may rely on the reading protein YTHDF1 to affect the translation pathway of the HSD17B11 gene to regulate the formation of lipid droplets in EC cells, thereby promoting the development of EC. The understanding of the role of epitranscriptomics in the development of EC will lay a theoretical foundation for seeking new anticancer therapies.

12.
Chem Asian J ; 17(14): e202200377, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35491405

ABSTRACT

Generally, C3 N4 was widely used in the field of photocatalytic hydrogen production, but only few studies focused on electrocatalytic hydrogen production field in Ni/Co based systems. Herein, to investigate the enhanced HER property of C3 N4 , NiCo2 O4 @C3 N4 were fabricated successfully via a simple mixture method. With the introduction of C3 N4 , NiCo2 O4 @C3 N4 showed better HER property with small overpotential (89 mV, η10  mA cm-2 ), low Tafel slope (146 mV dec-1 ) and superior long-term stability, thereby indicating the excellent synergistic effect between NiCo2 O4 and C3 N4 . Besides, compared with NiCo2 O4 , the large electrochemically active surface areas of NiCo2 O4 @C3 N4 (ca. 126 cm2 ) indicated the abundant active sites, directly proofing the HER enhancement of C3 N4 . According to Density Functional Theory (DFT) calculation results, when NiCo2 O4 combined with C3 N4 , the EH2O* of NiCo2 O4 @C3 N4 decreased from 3.80 to 2.76 eV and, accordingly, the heterostructure possessed an appropriate ΔGH* (0.19 eV, close to Pt), suggesting the unique synergistic effect between NiCo2 O4 and C3 N4 . Meanwhile, H2 O interacted with the d orbital of the Co atom and induced more electrons to transfer from NiCo2 O4 to C3 N4 and H2 O sequentially, thereby accumulating plenty of electrons on H2 O molecule and further activating H2 O molecule. Accordingly, the H-O-H bond angle of H2 O was narrowed from 104.3° to 103.2°, meanwhile, the O-H bond length was extended from 0.975 to 0.989 Å, demonstrating the HER enhancement of C3 N4 .

14.
Cytotherapy ; 24(5): 526-533, 2022 05.
Article in English | MEDLINE | ID: mdl-35219583

ABSTRACT

BACKGROUND AIMS: In this retrospective clinical study, the authors investigated the impact of cytokine-induced killer (CIK) cell-based immunotherapies on the long-term survival of patients with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 87 patients with ESCC who received comprehensive treatment were enrolled in the study. Of these patients, 43 were in the control group and 44 were in the CIK treatment group. Flow cytometry analysis was performed to detect the phenotype and anti-tumor function of CIK cells. Clinical characteristics were compared between these two groups, and the survival estimates of ESCC patients were determined using Kaplan-Meier analysis. RESULTS: CIK cells contained a high proportion of the main functional fraction (CD3+CD56+ group) and exhibited a strong killing ability for esophageal cancer cells in vitro. Importantly, overall survival (OS) and progression-free survival (PFS) were significantly higher in the CIK group than in the control group in early-stage ESCC. However, patients with advanced-stage ESCC did not benefit from CIK cell-based therapy in terms of OS and PFS compared with the control group. CONCLUSIONS: These results demonstrate that CIK cells combined with conventional treatments potentially prolong long-term survival of patients and may serve as a combined therapeutic approach for the treatment of early-stage ESCC.


Subject(s)
Cytokine-Induced Killer Cells , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Combined Modality Therapy , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/therapy , Humans , Immunotherapy , Immunotherapy, Adoptive/methods , Retrospective Studies , Treatment Outcome
16.
Eur J Immunol ; 52(2): 338-351, 2022 02.
Article in English | MEDLINE | ID: mdl-34755333

ABSTRACT

PSMA3, a member of the proteasome subunit, has been shown to play a major player in protein degradation. Reportedly, PSMA3 functions as a negative regulator in various cancers including colon, pancreatic and gastric cancers. However, the contributions of PSMA3 to the progression of esophageal squamous cell carcinoma (ESCC) and the underlying mechanism remain unclear. Therefore, in this study, we investigated whether PSMA3 is involved in ESCC progression and the potential underlying mechanism. The results revealed that PSMA3 was highly expressed in the ESCC tumor tissues and functioned as a negative indicator according to the data from The Cancer Genome Atlas (TCGA)/Gene Expression Omnibus (GEO) datasets and clinical patients' samples. Pathway enrichment analysis showed that PSMA3 was closely correlated with ESCC cancer stemness and the inflammatory response; however, this correlation was absent after knockdown of PSMA3 in vitro. We further demonstrated that PSMA3 suppressed CD8+ T-cells infiltration depending on the C-C motif chemokine ligand 3 (CCL3)/C-C motif chemokine receptor 5 (CCR5) axis. Collectively, these results demonstrate the role of PSMA3 in ESCC cancer stemness and the negative regulation of CD8 T-cells infiltration mediated by PSMA3. The results of this study may provide a potential target for the immuno-oncology effect of PSMA3 in ESCC therapy.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Gene Expression Regulation, Enzymologic/immunology , Gene Expression Regulation, Neoplastic/immunology , Neoplasm Proteins , Cell Line, Tumor , Databases, Nucleic Acid , Esophageal Neoplasms/enzymology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/immunology , Esophageal Squamous Cell Carcinoma/enzymology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/immunology , Humans , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Neoplasm Proteins/immunology , Proteasome Endopeptidase Complex/biosynthesis , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/immunology
17.
J Hematol Oncol ; 14(1): 187, 2021 11 06.
Article in English | MEDLINE | ID: mdl-34742349

ABSTRACT

Complex interactions between the immune system and tumor cells exist throughout the initiation and development of cancer. Although the immune system eliminates malignantly transformed cells in the early stage, surviving tumor cells evade host immune defense through various methods and even reprogram the anti-tumor immune response to a pro-tumor phenotype to obtain unlimited growth and metastasis. The high proliferation rate of tumor cells increases the demand for local nutrients and oxygen. Poorly organized vessels can barely satisfy this requirement, which results in an acidic, hypoxic, and glucose-deficient tumor microenvironment. As a result, lipids in the tumor microenvironment are activated and utilized as a primary source of energy and critical regulators in both tumor cells and related immune cells. However, the exact role of lipid metabolism reprogramming in tumor immune response remains unclear. A comprehensive understanding of lipid metabolism dysfunction in the tumor microenvironment and its dual effects on the immune response is critical for mapping the detailed landscape of tumor immunology and developing specific treatments for cancer patients. In this review, we have focused on the dysregulation of lipid metabolism in the tumor microenvironment and have discussed its contradictory roles in the tumor immune response. In addition, we have summarized the current therapeutic strategies targeting lipid metabolism in tumor immunotherapy. This review provides a comprehensive summary of lipid metabolism in the tumor immune response.


Subject(s)
Lipid Metabolism , Neoplasms/immunology , Tumor Microenvironment , Animals , Humans , Immunity , Immunotherapy , Neoplasms/metabolism , Neoplasms/therapy , Tumor Escape
18.
Signal Transduct Target Ther ; 6(1): 372, 2021 10 27.
Article in English | MEDLINE | ID: mdl-34707085

ABSTRACT

Varying differentiation of myeloid cells is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. The release of cytokines from myeloid cells is an important driving factor that leads to severe COVID-19 cases and subsequent death. This review briefly summarizes the results of single-cell sequencing of peripheral blood, lung tissue, and cerebrospinal fluid of COVID-19 patients and describes the differentiation trajectory of myeloid cells in patients. Moreover, we describe the function and mechanism of abnormal differentiation of myeloid cells to promote disease progression. Targeting myeloid cell-derived cytokines or checkpoints is essential in developing a combined therapeutic strategy for patients with severe COVID-19.


Subject(s)
COVID-19/immunology , Cell Differentiation/immunology , Cellular Microenvironment/immunology , Myeloid Cells/immunology , SARS-CoV-2/immunology , Animals , COVID-19/therapy , Humans , Myeloid Cells/virology , Single-Cell Analysis
19.
Angew Chem Int Ed Engl ; 60(44): 23596-23601, 2021 Oct 25.
Article in English | MEDLINE | ID: mdl-34490686

ABSTRACT

Polyperylenediimide (PDI) is always subject to its modest conductivities, limited reversible active sites and inferior stability for potassium storage. To address these issues, herein, we firstly propose an organic-inorganic hybrid (PDI@Fe-Sn@N-Ti3 C2 Tx ), where Fe/Sn single atoms are bound to the N-doped MXenes (N-Ti3 C2 Tx ) via the unsaturated Fe/Sn-N3 bonds, and functionalized with PDI via d-π hybridization, forming a high conjugated δ skeleton. The resulted hybrid cathode endowed with enhanced electronic/ionic conductivities, lowered dissociation barriers of multiple redox centers and a stable cathode electrolyte interphase layer displays a 14-electron involved high-rate capacities and long cycle life. Moreover, it shows competitive performance in full cells even under different folding states and low operating temperatures.

20.
Front Immunol ; 12: 680055, 2021.
Article in English | MEDLINE | ID: mdl-34194433

ABSTRACT

Background: There is increasing evidence that group 2 innate lymphoid cells (ILC2s) play an essential role in allergy and parasitic infection. However, the role of ILC2s in human lung cancer remains unclear. Methods: ILC2s from peripheral blood mononuclear cells (PBMCs) obtained from healthy donors (HDs) and non-small cell lung cancer (NSCLC) patients, and NSCLC tumor tissues were analyzed via multicolor flow cytometry. ILC2s or CD14+ cells were sorted by fluorescence-activated cell sorting. qPCR and flow cytometry were performed to assess the gene and protein expression of the indicated molecules. M1-like and M2-like macrophages were induced from CD14+ monocytes in vitro. Results: ILC2s were significantly more enriched in PBMCs and tumor tissues from NSCLC patients than in HDs. After screening for the main immune checkpoint molecules, we found that PD-1 was upregulated in ILC2s in NSCLC patients. Functionally, PD-1high ILC2s from tumor tissues expressed higher levels of IL-4 and IL-13 regarding both mRNA and protein levels than PD-1low ILC2s. Furthermore, PD-1high ILC2s robustly boosted M2-like macrophage polarization in vitro, by secreting IL-4 and IL-13, while neutralization of IL-4 and IL-13 by antibodies abrogated M2-like macrophage polarization. Conclusion: ILC2s are enriched in NSCLC patients and upregulate PD-1 expression. Upregulation of PD-1 facilitates the immunosuppressive function of ILC2s. PD-1high ILC2s enhance M2-like macrophage polarization by secreting IL-4 and IL-13. PD-1 acts as a positive regulator of the immunosuppressive function of ILC2s in human NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/metabolism , Immunity, Innate , Lung Neoplasms/etiology , Lung Neoplasms/metabolism , Lymphocytes/immunology , Lymphocytes/metabolism , Programmed Cell Death 1 Receptor/metabolism , Biomarkers , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cytokines/metabolism , Female , Humans , Immunomodulation , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Macrophage Activation , Macrophages/immunology , Macrophages/metabolism , Male , Signal Transduction
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