Expression and Clinical Significance of CLCA2 in Pan-Cancer

SUMMARY: The calcium-activated chloride channel (CLCA2) performs a vital function in the intricate process of tumorigenesis. Using a bioinformatics analysis system, we conducted a pan-cancer investigation on CLCA2 to explore its association with tumor prognosis and its involvement in immunology. In order to achieve this objective, we examined the prognostic significance and expression level of CLCA2 in multiple cancer types using the TIMER and Sangerbox databases. The analysis of protein interaction networks revealed proteins linked to CLCA2. To investigate the potential biological functions and enrichment pathways of CLCA2 in cancer, the SangerBox and GSCA databases were utilized. Furthermore, the expression of CLCA2 in different cancer subtypes was evaluated during the analysis. Various functional conditions of cancer cells were then compared with CLCA2 in the CancerSEA database. Using online tools like TISIDB and Assistant for Clinical Bioinformatics, the investigation explored the link between CLCA2 and immune subtypes. Additionally, it assessed immune cell infiltration as part of the analysis. In addition, the application of GDSA was employed to investigate the predictive significance of CLCA2 in relation to drug sensitivity. The research outcomes uncovered abnormal expression patterns of CLCA2 in diverse tumor categories, with its expression level demonstrating a correlation with distinct subtypes of tumors. Strong associations have been observed between enhanced patient survival rates and CLCA2 in specific tumor types. There is a noteworthy connection observed among diverse tumor types, immune cell infiltration, immune subtypes, and CLCA2. The enrichment analysis of KEGG indicates that there may exist a connection between the expression of CLCA2 and renin secretion, pancreatic secretion, as well as other pathways in pan-cancer. CLCA2 appears to primarily activate pathways such as EMT (epithelial-mesenchymal transition), RAS/MAPK, RTK, apoptosis, TSC/mTOR, and PI3K/ AKT in pan-cancer. On the other hand, it seems to inhibit pathways like cell cycle, DNA damage, hormone AR, and hormone ER. Through single-cell functional analysis, it has been confirmed that CLCA2 is associated with diverse cellular functional states, encompassing DNA repair, EMT, hypoxia, invasion, metastasis, and quiescence. Furthermore, a substantial correlation has been observed between the expression of CLCA2 and drug sensitivity towards bosutinib, tipifarnib-P1, as well as other therapeutic agents. This research affirms that various cancer types express CLCA2 and its involvement in tumor advancement and immune penetration. CLCA2 possesses the capability to function as a noteworthy biomarker and target for therapeutic intervention in diverse cancer forms.

El canal de cloruro activado por calcio (CLCA2) desempeña una función vital en el proceso de tumorigénesis. Utilizando un sistema de análisis bioinformático, llevamos a cabo una investigación pan-cáncer en CLCA2 para explorar su asociación con el pronóstico tumoral y su participación en la inmunología. Para lograr este objetivo, examinamos la importancia pronóstica y el nivel de expresión de CLCA2 en múltiples tipos de cáncer utilizando las bases de datos TIMER y Sangerbox. El análisis de las redes de interacción de proteínas reveló proteínas vinculadas a CLCA2. Para investigar las posibles funciones biológicas y las vías de enriquecimiento de CLCA2 en el cáncer, se utilizaron las bases de datos SangerBox y GSCA. Además, durante el análisis se evaluó la expresión de CLCA2 en diferentes subtipos de cáncer. Luego se compararon varias condiciones funcionales de las células cancerosas con CLCA2 en la base de datos CancerSEA. Utilizando herramientas en línea como TISIDB y Assistant for Clinical Bioinformatics, la investigación exploró el vínculo entre CLCA2 y los subtipos inmunes. Además, evaluó la infiltración de células inmunitarias como parte del análisis y se empleó la aplicación de GDSA para investigar la importancia predictiva de CLCA2 en relación con la sensibilidad al fármaco. Los resultados de la investigación descubrieron patrones de expresión anormales de CLCA2 en diversas categorías de tumores, y su nivel de expresión demuestra una correlación con distintos subtipos de tumores. Se han observado fuertes asociaciones entre mayores tasas de supervivencia de los pacientes y CLCA2 en tipos de tumores específicos. Se observa una conexión notable entre diversos tipos de tumores, infiltración de células inmunitarias, subtipos inmunitarios y CLCA2. El análisis de enriquecimiento de KEGG indica que puede existir una conexión entre la expresión de CLCA2 y la secreción de renina, la secreción pancreática y otras vías en el pancáncer. CLCA2 parece activar principalmente vías como EMT (transición epitelial-mesenquimatosa), RAS/MAPK, RTK, apoptosis, TSC/mTOR y PI3K/AKT en pan-cáncer. Por otro lado, parece inhibir vías como el ciclo celular, el daño del ADN, la hormona AR y la hormona ER. Mediante análisis funcional unicelular, se ha confirmado que CLCA2 está asociado con diversos estados funcionales celulares, que abarcan la reparación del ADN, la EMT, la hipoxia, la invasión, la metástasis y la inactividad. Además, se ha observado una correlación sustancial entre la expresión de CLCA2 y la sensibilidad al fármaco hacia bosutinib, tipifarnib-P1, así como a otros agentes terapéuticos. Esta investigación indica que varios tipos de cáncer expresan CLCA2 y su participación en el avance tumoral y la penetración inmune. CLCA2 posee la capacidad de funcionar como un biomarcador notable y como un objetivo para la intervención terapéutica en diversas formas de cáncer.

Research progress on mitochondria regulating anti-tumor immunity / 浙江大学学报·医学版

Tumor cells adaptively reforge their metabolism to meet the demands of energy and biosynthesis. Mitochondria, pivotal organelles in the metabolic reprogramming of tumor cells, contribute to tumorigenesis and cancer progression significantly through various dysfunctions in both tumor and immune cells. Alterations in mitochondrial dynamics and metabolic signaling pathways exert crucial regulatory influence on the activation, proliferation, and differentiation of immune cells. The tumor microenvironment orchestrates the activation and functionality of tumor-infiltrating immune cells by reprogramming mitochondrial metabolism and inducing shifts in mitochondrial dynamics, thereby facilitating the establishment of a tumor immunosuppressive microenvironment. Stress-induced leakage of mitochondrial DNA contributes multifaceted regulatory effects on anti-tumor immune responses and the immunosuppressive microenvironment by activating multiple natural immune signals, including cGAS-STING, TLR9, and NLRP3. Moreover, mitochondrial DNA-mediated immunogenic cell death emerges as a promising avenue for anti-tumor immunotherapy. Additionally, mtROS, a crucial factor in tumorigenesis, drives the formation of tumor immunosuppressive microenvironment by changing the composition of immune cells within the tumor microenvironment. This review focuses on the intrinsic relationship between mitochondrial biology and anti-tumor immune responses from multiple angles. We expect to explore the core role of mitochondria in the dynamic interplay between the tumor and the host, in order to facilitate the development of targeted mitochondrial strategies for anti-tumor immunotherapy.

Cell-to-Cell Communications of cGAS-STING Pathway in Tumor Immune Microenvironment / 浙江大学学报·医学版

Targeting cGAS-STING pathway is a promising strategy in tumor treatment. The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of the second messenger 2'3'-cGAMP, activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING. Notably, in tumor immune microenvironment, key components of cGAS-STING pathway are transferred among neighboring cells. The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity. The membrane-based system, including extracellular vesicles transport, phagocytosis and membrane fusion transmit dsDNA, cGAMP and activated STING, enhancing the immune surveillance and inflammatory. The membrane proteins, including specific protein channel and intercellular gap junctions, transfer cGAMP and dsDNA, which are crucial to regulate immune responses. And the ligand-receptor interactions for interferons transmission amplifies the anti-tumor response. This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment. We further explore how these mechanisms modulate immunological processes and discuss potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Research progress of small molecule modulators targeting Toll-like receptor 2 / 药学学报

Toll like receptors (TLRs) are the earliest discovered natural immune pattern recognition receptors (PRRs). The abnormality of TLR signal transduction pathway is the key factor leading to chronic inflammatory, cancer, nervous system disease and cardiovascular diseases. The development of TLR agonists and inhibitors has attracted much attention. Currently known TLR2 agonists, such as lipopeptides or their derivatives, have certain limitations in drug development due to their difficult synthesis, easy hydrolysis, and triggering inflammatory cytokine storms, while inhibitors have been rarely reported. New small molecule TLR2 agonists or inhibitors with higher stability are more likely to be developed as tumor immunotherapy or anti-inflammatory drugs.

Salvianolic acid B exerts its anti-tumor immunity by targeting USP2 and reducing the PD-L1 level / 药学学报

With the development of small-molecule immunotherapy drugs, its combination with the programmed cell death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibodies would provide a new opportunity for cancer treatment. Therefore, targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity and considered as the next generation of tumor immunotherapy. In the present study, we investigated the anti-tumor role of salvianolic acid B (SAB) by regulating the PD-L1 level in tumors. Changes of total PD-L1 and membrane PD-L1 levels were determined by Western blot, flow cytometry and PD-1/PD-L1 interaction assays. The expression of mRNA level of PD-L1 was detected by real-time PCR. The cytotoxicity of activated peripheral blood mononuclear cell (PBMC) cells toward co-cultured tumor cells was measured by cell impedance assay and crystal violet experiment. Surface plasma resonance technique was used to analyze the direct interaction between SAB and ubiquitin carboxyl-terminal hydrolase 2 (USP2). The antitumor effect of SAB in vivo was examined by C57BL/6 mice bearing MC38 xenograft tumor (all animal experiments were conducted in accordance with the Animal Ethics Committee of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences). Western blot and flow cytometry assay showed that SAB can significantly downregulate the abundance of PD-L1 in RKO and PC3 cells in dose- and time-dependent manner. PD-1/PD-L1 binding assay revealed that SAB reduces the binding of tumor cells to recombinant PD-1 protein. Mechanism studies revealed that SAB can bind directly to USP2 protein and inhibit its activity, thus promote the ubiquitin-proteasome pathway degradation of PD-L1 proteins. In addition, Cell impedance and crystal violet staining indicated that SAB enhances the killing activity of co-cultured PBMC cells toward tumor cells. MC38 tumor transplanted mouse experiments revealed that SAB treatment displayed significant suppression in the growth of MC38 tumor xenografts in C57BL/6 mice with an inhibition rate of 63.2% at 20 mg·kg-1. Our results demonstrate that SAB exerts its anti-tumor activity by direct binding and inhibiting the activity of USP2 and reducing the PD-L1 level. Our study provides an important material basis and scientific basis for the potential application of SAB in tumor immunotherapy drug targeting USP2-PD-L1 axis.

Biological Functions of CD24 in Malignant Tumor and its Application as a Novel Anti-tumor Target / 中国生物化学与分子生物学报

CD24 is a highly glycosylated protein that is linked to the plasma membrane via a glycosylphosphatidylinositol anchor. As a universally expressed protein on immune cells, CD24 is also overexpressed in nearly 70% of human cancers including hepatocellular carcinoma, lung cancer and bladder cancer et al. Studies revealed that CD24 is involved in regulating cell proliferation, migration and invasion in cancer cells by interacting with P-selectin, activating Wnt and MAPK signaling pathway or other signaling molecules. Therefore, CD24-targeted siRNA or antibody has a great potential to exert anti-tumor effects by blocking the interaction. There are currently several agents or regiments targeting CD24 for the treatment of patients with various kinds of cancers that are undergoing assessment in the preclinical study at present. Recent studies revealed that CD24 was able to interact with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which located on the surface of macrophages, to compose a novel immune checkpoint. The binding of CD24 to Siglec-10 elicits an inhibitory signaling cascade, limits macrophage phagocytosis, evades immune surveillance, and promotes tumor growth, which suggested that CD24 may be a potential target in anti-tumor immunotherapy. In this review, we introduced the structure and function of CD24 and its role in cancer progression and anti-tumor immunity. Moreover, the progression in developing novel anti-cancer drugs or treatment strategies with the target of CD24 was summarized, which aims to provide a new insight in CD24-targeting therapy.

Shuyuwan Regulates M1/M2 Polarization of Tumor-associated Macrophages to Inhibit Progression of Colorectal Cancer / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of Shuyuwan regulating polarization of tumor-associated macrophages （TAMs） to inhibit the progression of colorectal cancer （CRC）. MethodThe nude mouse model of orthotopic transplantation of colon cancer was established. Male BALB/c-nu nude mice （n=28， 4 weeks old） were randomly assigned into 4 groups （n=7）： Model group （normal saline） and low-， medium-， and high-dose （1.725， 2.310， 2.895 g·kg-1·d-1， respectively） Shuyuwan groups. On day 9 after the tumor block was inoculated， the mice were administrated by gavage with corresponding agents at a dose of 15 mL·kg-1 once a day， 6 days a week， and no agent on the 7th day. After two consecutive weeks of intervention， the nude mice were sacrificed and the tumor samples were collected. A part of the colon tissue and the tumor tissue was used to prepare sections， and hematoxylin-eosin （HE） staining was performed for pathological observation. The expression of inducible nitric oxide synthase （iNOS） and arginase-1 （Arg-1） in the tumor tissue was detected by immunohistochemistry （IHC）. The mRNA levels of interleukin-12 （IL-12）， epidermal growth factor （EGF）， and transforming growth factor-β1 （TGF-β1） in the tumor tissue were determined by Real-time polymerase chain reaction （PCR）. Western blot was employed to determine the protein levels of iNOS， IL-12， EGF， and TGF-β1 in the tumor tissue. ResultCompared with the model group， Shuyuwan inhibited the growth of colon cancer cells in nude mice and caused the tumor cell necrosis in different degrees. The high-dose Shuyuwan group had the strongest inhibitory effect on the growth of tumor cells， which basically lost the normal morphology. Furthermore， Shuyuwan up-regulated the expression of iNOS and IL-12 in M1-type macrophages （P<0.05） and down-regulated the expression of Arg-1， EGF， and TGF-β1 in M2-type macrophages （P<0.05）， which indicated the weakened polarization of macrophages toward M2 type and the enhanced polarization toward M1 type after treatment with Shuyuwan. ConclusionShuyuwan can inhibit the growth of orthotopically transplanted colon tumor by blocking the polarization of TAMs to M2 type and promoting the polarization of TAMs to M1 type.

Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine / 中国药科大学学报

@#Several programmed cell death protein 1 (PD-1) or its ligand (PD-L1) immune checkpoint blocking antibodies are available for clinical treatment, but only some patients show clinical response, so an alternative strategy for tumor immunotherapy is needed.A therapeutic tumor vaccine targeting PD-L1 is a meaningful attempt.In this study, we designed an epitope peptide vaccine targeting PD-L1, and then screened the immunogenic PD-L1 epitope peptide based on the humanized immune system (HIS) mouse model and further investigated its anti-tumor activity.The results show that the designed and screened PD-L1-B1 epitope peptide vaccine not only successfully induced PD-L1-specific humoral and cellular immunity, but also exhibit anti-tumor activity.In addition, immunotherapy increased T-lymphocyte infiltration of tumors and reshaped the tumor immunosuppressive microenvironment.In conclusion, PD-L1-B1 epitope peptide vaccine exhibits potent anti-tumor activity and may be an effective alternative immunotherapeutic strategy for patients insensitive to PD-1/PD-L1 blockade.

Tumor cell lysate with low content of HMGB1 enhances immune response of dendritic cells against lung cancer in mice / 南方医科大学学报

OBJECTIVE@#To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer.@*METHODS@#TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed.@*RESULTS@#The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05).@*CONCLUSION@#Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.

Macrophage-camouflaged epigenetic nanoinducers enhance chemoimmunotherapy in triple negative breast cancer

Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.

Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

Preclinical study of LMP1-RNAi-based anti-tumor therapy in EBV-positive nasopharyngeal carcinoma

RNA interference (RNAi) treatment has been proven to be an important therapeutic approach in cancer based on downregulation of target-oncogenes, but its clinical efficacy still needs further investigation. LMP1 is usually presented by Epstein-Barr virus (EBV)-positive tumor cells like EBV-associated nasopharyngeal carcinoma (NPC) and acts as an oncogene in tumorigenesis. However, the mechanism of LMP1 as a proto-oncogene in nasopharyngeal carcinoma is still unclear. Two sequence-specific shRNAs 1 and 2 were designed to target the different nucleotide loci of EBV latent antigen LMP1 gene and a series of in vivo and in vitro experiments were performed to investigate the therapeutic effect of sequence-specific shRNAs targeting LMP1 and its related molecular mechanisms in EBV-positive NPC. LMP1-shRNA2 generated a truncated LMP1 mRNA and protein, whereas LMP1-shRNA1 completely blocked LMP1 mRNA and protein expression. Both LMP1-shRNAs inhibited the proliferation and migration of NPC cells overexpressing LMP1 (NPC-LMP1) as well as the NPC-associated myeloid-derived suppressor cell (MDSC) expansion in vitro. However, LMP1-shRNA2 maintained the immunogenicity of NPC-LMP1 cells, which provoked MHC-class I-dependent T cell recognition. LMP1-shRNAs inhibited tumor growth in nude mice but did not reach statistical significance compared to control groups, while the LDH nanoparticle loaded LMP1-shRNAs and the antigen-specific T cells induced by NPC-LMP1 cells treated with LMP1-shRNA2 significantly reduced tumor growth in vivo. LMP1-RNAi-based anti-tumor therapy could be a new hope for the clinical efficacy of RNAi treatment of tumors like NPC.

Tetrahedral DNA nanostructures synergize with MnO2 to enhance antitumor immunity via promoting STING activation and M1 polarization

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.

Progress in differentiation regulation and subpopulation typing of exhausted CD8 + T cells / 中华微生物学和免疫学杂志

Exhausted CD8 + T cells (CD8 + Tex) are a distinct subpopulation formed from naive CD8 + T cells under conditions of sustained high antigen stimulation. Initially, naive CD8 + T cells can differentiate into functional cytotoxic cells and exert anti-infective and anti-tumor effects upon short-term antigen stimulation. However, sustained high antigen stimulation will make effector CD8 + T cells progressively differentiate into terminally CD8 + Tex cells and irreversibly lose effector function. Unlike memory and effector T cells, CD8 + Tex cells have a unique transcriptional program. Numerous studies are attempting to map a detailed differentiation landscape of CD8 + Tex cell subsets, aiming to maximize the number of effector T cells in the future by targeting individual subsets or individual differentiation stages in CD8 + Tex cells without damaging the effector cells. This article reviewed the progress in CD8 + Tex cells from the aspects of transcriptional dysregulation, metabolic reprogramming, subpopulation typing and clinical application, aiming to provide more CD8 + T cell-based therapeutic strategies for tumor.

Research Progress on Hyperthermia and Anti-Tumor Immunity / 肿瘤防治研究

In recent years, with the development of comprehensive tumor therapy, hyperthermia has become one of the important means of cancer treatment. A large number of studies have shown that the removal of tumor cells depends on exogenous treatment methods and the body's own anti-tumor immune status. Hyperthermia cannot only directly kill tumor cells but also activate the body's immunity to exhibit an anti-tumor effect. In recent years, with the deepening of tumor research, hyperthermia has been able to create a type I tumor microenvironment with PD-L1 overexpression and enrichment of tumor-infiltrating lymphocytes, complementing the enhancement of immune checkpoint inhibitors. Hyperthermia combined with immunotherapy may offer a new perspective in cancer treatment. The mechanism of tumor hyperthermia and anti-tumor immunity and its clinical application have aroused great interest and become a new research field. This article reviews the relationship between tumor hyperthermia and anti-tumor immunity.

Research progresses on NLRP3 inflammasomes-induced anti-tumor immunity / 药学学报

More and more studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome has become the regulatory factor of inflammatory response and protective immunity, and the assembly and activation of NLRP3 inflammasomes are closely related to the anti-tumor immunity effect. Depending on the cell type and stimuli, activation of the NLRP3 inflammasome can induce immune cells to become polarized, hyperactive, or pyroptotic, releasing interleukin (IL)-1β and IL-18, which leads to cascade immune or inflammatory responses, and its role in tumor immunity has received extensive attention. Here, we review the mechanisms of the NLRP3 inflammasome enhancing CD8+ T cells-mediated anti-tumor immunity by inducing the pyroptosis of tumor cell, the pyroptosis or hyperactive state of dendritic cells (DCs), and the pyroptosis or polarization of the macrophages. Different anti-tumor immune roles of NLRP3 inflammasome activation in tumor cells and immune cells provide new directions for future research and may influence the development of next-generation immunotherapy.

Research progress on anti-tumor and tumor immunity of marine natural products / 药学学报

In recent years, the oceans have provided an important source of highly promising new anti-tumor drugs for innovation and screening, with approximately 56% of biologically active compounds being discovered to have anti-tumor effects each year. In this study, we classified and summarized the approved drugs of marine origin in terms of anti-tumor therapy, and firstly, we briefly overviewed the role of the immune system in cancer pathogenesis and discussed the current dilemma of cancer immunotherapy and highlighted the main anti-tumor targets of marine drugs. Further, with a focus on tumor immunity, we classified and outlined the history of currently approved marine original drugs by species origin, structural features, relevant pathways, and clinical application and therapy. Lastly, the limitations of current marine drug research were discussed, as well as prospects and trends in new drug development.

Research Status of Tumor-associated Fibroblasts Regulating Immune Cells / 中国肺癌杂志

Cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells are the most essential components of the tumor microenvironment (TME). They communicate with each other in tumor microenvironment and play a critical role in tumorigenesis and development. CAFs are very heterogeneous and different subtypes of CAFs display different functions. At the same time, it can contribute to the regulation of the function of tumor-infiltrating immune cells and eventually result in the carcinogenesis, tumor progression, invasion, metastasis and other biological behaviors of tumors by producting various growth factors and cytokines etc. Based on the current research results at home and abroad, this paper reviews the recent research progress on the regulation of CAFs on infiltrating immune cells in tumor microenvironment.
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Effect of Decitabine on Regulatory T Cells Relative Content in Peripheral Blood and Bone Marrow of Patients with Myelodysplastic Syndrome/Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate regulatory T cells (Tregs) relative content in peripheral blood and bone marrow of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with or without decitabine (DAC), analyze the immunomodulatory of Tregs in pathogenesis and remission of MDS and AML, as well as effect of DAC on Tregs.@*METHODS@#From October 2018 to February 2019, 15 patients with MDS and 49 patients with AML (newly diagnosed, treated with DAC or other chemotherapy regimens) were enrolled in this study, and 14 cases with iron deficiency or megaloblastic anemia while without malignant tumor and autoimmune disease as controls. The Tregs relative contents in bone marrow and peripheral blood were analyzed by flow cytometry, meanwhile clinical data of the objects were collected.@*RESULTS@#In peripheral blood and bone marrow of the patients with MDS and AML, the Tregs relative contents at newly diagnosed were higher than those of the control group (P=0.05, P=0.043). The Tregs relative content of AML patients in DAC regimen treatment group was significantly lower than that in the newly diagnosed group and non-DAC chemotherapy group (P<0.05). In DAC regimen treatment group, the Tregs relative contents was significantly lower in remission group than in non-remission group (P<0.05). There was no difference between DAC regimen treatment group and control group in Tregs relative content.@*CONCLUSION@#DAC may increase the body's anti-tumor immunity by consuming Tregs content, enhance the body's immune function to identify and kill tumor cells, thereby promote the patients' reliefs.

Opportunities and challenges for the clinical application of multi-parameter flow cytometry in the era of chimeric antigen receptor-modified T cell immunotherapy / 中华检验医学杂志

Chimeric Antigen Receptor-modified(CAR)-T cells have become a new star living cell "drug" in the field of tumor immunotherapy, and five drugs have been available to the public since 2017. The favourable, rapid and efficient interaction of CAR-T therapy from bench to bedside has solved many new scientific problems, which remarkably expands the application field of multi-parameter flow cytometry (MFC). MFC participates the whole process of CAR-T preparation, functional evaluation, quality control, in vivo continuation evaluation, clinical efficacy and toxicity monitoring. New clinical problems caused by high-precision targeted therapy of CAR-T cells pose new challenges in using MFC for accurate tumor immunophenotyping, minimal residual disease monitoring, as well as the demands of comprehensively evaluation of the systematic immune function in different disease stages. In the era of targeted therapy, timely communication between laboratories and clinics is particularly important for obtaining accurate MFC results, which assists clinical individualized diagnosis and treatment.