727 results about "Immunosuppression" patented technology

The invention belongs to the cross technical field of nanomedicine, tumor treatment and immunotherapy, and particularly provides tumor mitochondria-targeted copper death selective induction nanoparticles, which are prepared by the following preparation method: S1, specifically coupling TPY and MHI through condensation reaction to obtain MTPY; s2, MTPY and copper ions are subjected to complexation, and an MTPY-Cu complex is obtained; and S3, the MTPY-Cu complex and albumin are subjected to self-assembly, and the MTPY-Cu-coated Alb nanoparticles are formed. The dosage of copper is only 1 / 1000 of that of free Cu < 2 + >, and equivalent immune regulation and killing effects can be achieved; primary tumors and distant tumor focuses can be inhibited, and lung metastasis is reduced; immune memory can be induced, and relapse can be prevented; the traditional Chinese medicine composition is combined with cis-platinum to remarkably enhance the curative effect and reverse the induced immunosuppression; the invention has the advantages of high biological safety and no obvious liver and kidney toxicity or hemolytic reaction.

The invention belongs to the technical field of biology, and particularly relates to a cryptosporidium parvum infection immunosuppression mouse model and a construction method thereof. Aiming at the problem that the development of cryptosporidiosis drugs and vaccines is seriously limited due to the fact that no model for successfully infecting mice with cryptosporidium parvum exists at present, the invention provides the construction method of the cryptosporidium parvum infection immunosuppression mouse model, which comprises the following steps: firstly, carrying out gavage treatment on the mice for 4-7 days by adopting cyclophosphamide; constructing to obtain an immunosuppressive mouse; feeding PBS (Phosphate Buffer Solution) containing cryptosporidium parvum oocysts through the mouth, and infecting for 7-21 days; and when oocysts are continuously detected from excrement of the mouse and the content of the oocysts is higher than the infection amount, constructing the cryptosporidium parvum infection immunosuppression mouse model. The cryptosporidium parvum infection immunosuppression mouse model is successfully constructed, can be used for subsequent drug and vaccine development tests for cryptosporidium parvum diseases, and has a good application prospect.

The invention discloses a preparation method of a doxorubicin-loaded ginseng selenium polysaccharide nano-carrier with immunoregulation and liver cancer cell inhibition functions, and aims to solve the problems of toxic injury of tissues and organs and inhibition of an immune system caused by an antitumor drug doxorubicin. According to the invention, deoxycholic acid is grafted on the ginseng selenium polysaccharide, so that the ginseng selenium polysaccharide is hydrophobized and forms an amphiphilic polysaccharide polymer, and the limitations of large molecular weight, low bioavailability and the like of the ginseng selenium polysaccharide are overcome. The self-assembled ginseng selenium polysaccharide nanoparticles are used as carriers for delivering antitumor drugs, so that the self-assembled ginseng selenium polysaccharide nanoparticles have an immunoregulation effect and can effectively improve side effects such as immunosuppression caused by the antitumor drugs; and the carrier also has a pH sensitive response release characteristic, so that the targeting effect of the medicine in a tumor area is enhanced, and the innovative carrier has a good clinical application prospect.

The art does not provide systematic and reproducible methods to personalize dosing of multiple immunosuppressive medications after transplantation. This invention provides a method to systematize multi-drug immuno suppression management in tissue and organ transplantation using an artificial intelligence-based complex systems approach. In embodiments of this invention, immunosuppression drug dose, blood drug concentrations, donor-derived fraction of cell free DNA (dd-cfDNA %), and aspartate aminotransferase are used to indicate allograft status or a proxy for allograft status, to generate a phenotypic response surface to produce individual treatment modalities and dosages using empirically determined unique coefficients. This surface is used to calculate appropriate immunosuppression drug doses associated with the desired outcome for that patient. Embodiments of this disclosure are directed to identifying optimized combinations of inputs for the complex system of the immunosuppressed transplant patient in order to avoid transplant rejection while avoiding unnecessary toxicity and maintaining a robust enough immune response to fight infection.

The invention relates to the technical field of microorganisms, and discloses a lactobacillus delbrueckii subsp. Bulgaricus XJFY201503 and an application thereof in improving an immune function, the lactobacillus delbrueckii subsp. Bulgaricus XJFY201503 is preserved in the China General Microbiological Culture Collection Center (CGMCC), the preservation number is CGMCC NO.30047, and the preservation time is March 18, 2024. The lactobacillus delbrueckii subsp. Bulgaricus XJFY201503 can be used for directly improving the immune function of an immunosuppressive mouse by protecting and maintaining normal physiological structures of central and peripheral immune organs and promoting secretion of serum cytokines and immune globulins; and the immune function of the mouse can be indirectly promoted by relieving intestinal inflammation reaction.

The invention discloses a double-target chimeric antigen receptor for co-expression of CD47 and IL-15, a CAR-T cell and application of the CAR-T cell, and belongs to the technical field of genetic engineering, the double-target chimeric antigen receptor comprises a single-chain antibody scFv-EGFRv III, a single-chain antibody scFv-VEGF, CD47 and IL-15; the nucleotide artificial sequence of the single-chain antibody scFv-EGFRv III is as shown in SEQ ID NO. 6; the nucleotide artificial sequence of the single-chain antibody scFv-VEGF is as shown in SEQ ID NO. 9. According to the application disclosed by the invention, by performing sequence optimization on targets EGFRvIII and VEGF, the anti-tumor effect of CAR-T cells in glioblastoma can be improved, and by integrating immune checkpoint molecules CD47 and interleukin-15, the immunosuppression function of a CD47-SIRP alpha signal channel can be locally exerted.

The invention relates to the field of biological medicines, in particular to a chimeric cytokine activated receptor for activating lymphocytes by using soluble immunosuppressive molecules and application of the chimeric cytokine activated receptor in tumor treatment. The chimeric cytokine activation receptor and a chimeric antigen receptor for recognizing tumor antigens are connected in parallel to form a co-expressed polycistron structure. Wherein the chimeric cytokine activation receptor comprises an scFv structural domain, a transmembrane structural domain and a cytokine chimeric activation structural domain which specifically recognize and bind soluble immunosuppressive molecules. The CAR-NK cell can specifically recognize soluble inhibitory factors in the tumor microenvironment and improve the in-vivo and in-vitro anti-tumor efficacy of the CAR-NK cell, and can be used for treating solid malignant tumors.

The invention relates to the technical field of genetic engineering and biological agents, in particular to a hybrid peptide with immunoregulation and anti-oxidation functions and a preparation method and application of the hybrid peptide. The polypeptide provided by the invention has immunoregulation and antioxidation functions at the same time, and in a normal or immunosuppression state, the polypeptide can significantly improve the immunologic function of a body and reduce the damage of immunosuppression to the body; the oxidation resistance of cells and organisms can be enhanced; meanwhile, the polypeptide has the advantages of low cytotoxicity, high safety, simplicity and convenience in preparation and low cost, can be used as an ideal immunomodulator and an antioxidant, is widely applied to the fields of medicines, foods, health care, feeds, nutrition and the like of human and animals, and has very good application potential and value.

The present invention relates to the use of cannabidiol (CBD) in the treatment of patients with childhood-onset epilepsy who are concurrently taking immunosuppressant drugs. In particular the immunosuppressant drug is a calcineurin inhibitor. More particularly the immunosuppressant drug is tacrolimus. Where the CBD is used in combination with an immunosuppressant drug, caution should be taken. For example, the dose of either the CBD and / or the immunosuppressant drug may be required to be reduced. Moreover, the patient may need to be monitored for side effects of said drug-drug interaction. Preferably the CBD used is in the form of a highly purified extract of cannabis such that the CBD is present at greater than 98% of the total extract (w / w) and the other components of the extract are characterised. In particular the cannabinoid tetrahydrocannabinol (THC) has been substantially removed, to a level of not more than 0.15% (w / w) and the propyl analogue of CBD, cannabidivarin, (CBDV) is present in amounts of up to 1%. Alternatively, the CBD may be a synthetically produced CBD.

The invention relates to the technical field of nano-drug presentation systems, in particular to a TCR (T cell receptor) nano-vesicle antibody with both T cell redirection and immunosuppression reversal as well as a preparation method and application of the TCR nano-vesicle antibody. The TCR nano-vesicle antibody comprises a vesicle formed by a liposome and a cell membrane; tCR protein, a PD-1 antibody and a CD3 antibody are loaded on the vesicles. The nano vesicle antibody has the functions of T cell redirection and immunosuppression reversion; the difficulty of low stability of the soluble TCR is overcome; the polypeptide can be rapidly enriched in tumor tissues through tumor specificity TCR, and CD8 + T cells infiltrated by tumors are directly activated through an anti-CD3 antibody; depletion of T cells can be reversed through the PD-1 antibody on the surface, and the effector function of tumor infiltration CD8 + T cells is improved. The technical scheme can solve the technical problems that the TCR stability is not ideal and the immunosuppression state of the tumor microenvironment is difficult to overcome, and has ideal application and popularization prospects.

The invention discloses an engineered NK cell and a preparation method thereof. The antitumor activity of the NK cell is enhanced through synergistic modification of a fusion polypeptide and an anti-TIGIT monoclonal antibody. The amino acid sequence of the fusion polypeptide is shown as SEQ ID NO.1. The fusion polypeptide can specifically target tumor cells and activate the proliferation and killing functions of NK cells. And the anti-TIGIT monoclonal antibody further relieves the immunosuppression by blocking a TIGIT-CD155 signal channel. In-vitro experiments show that the killing rate of the combined modified NK cell on various solid tumors is obviously higher than that of the traditional CAR-NK cell. A PDX model shows that the engineered NK cells significantly inhibit tumor growth and enhance NK cell infiltration in a tumor microenvironment. The invention provides a new strategy with high efficiency and low toxicity for immunotherapy of solid tumors.

The present disclosure relates to 3-substituted 1,2,4-oxadiazole compounds and their derivatives, which are useful as V-domain immunoglobulin suppressor of T-cell activation (VISTA) inhibitors or as dual inhibitors of VISTA and the programmed cell death 1 (PD-1) signaling pathway. The disclosure also relates to treatment of disorders by inhibiting an immunosuppressive signal induced by VISTA and its ligands, PD-1, PD-L1, and / or PD-L2.

The invention discloses a function-enhanced mesenchymal stem cell preparation obtained by utilizing arthritis effusion and hypoxia pretreatment of mesenchymal stem cells as well as a preparation method and application of the function-enhanced mesenchymal stem cell preparation, and relates to the technical field of biological medicines. The preparation method of the function-enhanced mesenchymal stem cell preparation obtained by utilizing arthritis effusion and hypoxia pretreatment of mesenchymal stem cells comprises the following steps: S1, obtaining mesenchymal stem cells and performing hypoxia amplification passage; s2, pretreatment of arthritis effusion; S3, pre-stimulation of the arthritis effusion of the mesenchymal stem cells to obtain function-enhanced mesenchymal stem cells; s4, index detection and screening; s5, preparing a function-enhanced mesenchymal stem cell preparation; optimized low-oxygen pretreatment is adopted, so that the cell activity is improved; the mesenchymal stem cells subjected to joint pretreatment of arthritis effusion and hypoxia enhance expression and secretion of anti-inflammatory factors and immunomodulatory molecules in the cells; the pre-stimulated mesenchymal stem cells show a stronger immunosuppression function in vitro.

The invention relates to betulinic acid type saponin derivatives as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The structural general formula of the betulinic acid type saponin derivative is # imgabs0, R1 is selected from hydroxyl or-O-G, and G is monosaccharide; r2 is selected from dopamine, 5-aminovaleric acid, 4-aminobutyric acid or 3-aminopropionic acid and the like and salts thereof. The betulinic acid type saponin derivative does not show obvious cytotoxicity to THP-1 macrophages, and can obviously reduce the release of IL-6 and IL-1beta in the THP-1 macrophages induced by LPS (lipopolysaccharide). Compared with betulinic acid and positive control medicine mesalazine, the pharmaceutical composition has better anti-inflammatory activity, has the treatment effect of improving diarrhea and hemafecia of mice with colitis remarkably superior to those of betulinic acid and positive control medicine mesalazine, has the treatment effect of dermatitis superior to that of positive control medicine dexamethasone, and does not have obvious toxic or side effects such as weight loss and immunosuppression. Therefore, the betulinic acid type saponin derivative has good in-vivo and in-vitro safety and druggability.

The invention belongs to the technical field of biomedicine, and discloses a nano-particle for enhancing radioimmunotherapy effect through cascade reaction and application of the nano-particle, a preparation method of the nano-particle comprises the following steps: S1, synthesis of ZnO2; the preparation method comprises the following steps: dissolving ZnCl2 and PVP in absolute ethyl alcohol, adding ammonia water and H2O2, after the reaction is completed, collecting precipitates, washing, and dispersing the precipitates in absolute ethyl alcohol to prepare ZnO2; and S2, synthesis of ZnO2 (at) Cu: resuspending ZnO2 in water, sequentially adding ammonia water, a PAA solution, IPA, dopamine hydrochloride and a CuCl2 solution, stirring in a nitrogen atmosphere, centrifuging, washing with ethanol, and drying in vacuum to obtain the ZnO2 (at) Cu nano-particles, namely the nano-particles. According to the nanoparticles, the radiotherapy effect is enhanced through cascade reaction, copper death is induced, immune response is activated, effective treatment on tumors is achieved, and the problems of radiotherapy resistance and immunosuppressive tumor microenvironment are solved.

The invention provides a fermented beverage capable of relieving fatigue and a preparation method of the fermented beverage, and relates to the technical field of functional beverages, and the IPC classification number belongs to A23L2. The fermented beverage is prepared from a radix astragali fermentation extract, a radix platycodonis extract, L-arginine, taurine, inositol, caffeine, nicotinamide, vitamin B6, L-lysine hydrochloride, pyrroloquinoline quinone and auxiliary materials. The astragalus mongholicus fermentation extract can improve the ATP generation efficiency, reduce lactic acid accumulation after exercise, relieve damage of oxidative stress to muscle and nerve cells and reduce immunosuppression caused by fatigue; the platycodon grandiflorum extract has the effects of refreshing mind and restoring consciousness, improving cognitive function decline caused by central fatigue, enhancing capillary permeability and promoting removal of metabolic wastes. The radix astragali fermentation extract and the radix platycodonis extract are compounded to achieve a synergistic effect, so that the composition has an excellent anti-fatigue effect. Under the combined action of all the components, fatigue is relieved, energy is rapidly supplemented, and physical strength is recovered.

The invention discloses a preparation method and application of an ovotransferrin oligomer with an immunomodulatory effect, and a function enhanced nano oligomer is constructed through an enzymatic crosslinking and dynamic hot pressing synergistic treatment technology. The preparation method comprises the following specific steps: preparing an ovotransferrin solution, adjusting the pH value to 1.5-2.0, carrying out high-pressure homogenization and double-frequency ultrasonic treatment after pre-denaturation, adding TG enzyme to catalyze, crosslink and induce controllable aggregation, and finally freeze-drying to obtain oligomer powder, the oligomer is of a nano-scale spherical structure, the particle size is 50-200nm, the solubility is good, and the immunoregulation function is remarkably enhanced. Comprising the steps of promoting dendritic cells to secrete immune factors, prolonging the survival time of nematodes under bacterial infection and improving the immune function of immunosuppressive mice. The method disclosed by the invention is simple in process, green and environment-friendly, suitable for the fields of functional health-care products, pharmaceutical preparations, formula foods with special medical purposes and the like, and wide in application prospect.

The present invention relates to chimeric antigen receptors (CAR) against multiple but not all human leukocyte antigen (HLA-G) isoforms. More specifically, the invention concerns CARs that are specific for HLA-G β2M-free or β2M-associated immunosuppressive isoforms respectively.

The invention relates to the technical field of medicines, in particular to a composite nano vaccine and application thereof. The composite nano vaccine is prepared by coupling a natural compound with endoplasmic reticulum stress induction capability on the surface of Ga-MOF nano particles. The composite nano vaccine can significantly enhance the anti-tumor effect through a ferroptosis mechanism, an endoplasmic reticulum stress and immunogenic cell death mechanism and a cryoablation technology synergistic effect mechanism, reverses an immunosuppressed tumor microenvironment, inhibits the growth of primary tumors and distant metastatic tumors, and has a good anti-tumor effect. A brand new strategy is provided for comprehensive treatment of tumors, and the application prospect is wide.

The invention discloses a polyethylene glycol modified gold and manganese dioxide nano particle and a preparation method and application thereof, and belongs to the technical field of biological medicine, the polyethylene glycol modified gold and manganese dioxide nano particle (GMCN and PEG) has good biocompatibility under neutral physiological conditions, can relieve tumor hypoxia and increase generation of active oxygen in acidic TME, and has a good anti-tumor effect. The radiotherapy sensitivity is improved; and immune cell death is induced. Meanwhile, a cGAS-STING signal channel can be activated, dendritic cell maturation, macrophage M1 polarization and T cell infiltration are promoted, and the immunosuppression state in TME is counteracted. In addition, the GMCN-coated PEG also has an MR-CT bimodal imaging enhancement function, and integration of diagnosis and treatment is realized. The nano sensitizer disclosed by the invention has huge potential in the aspects of improving the radiotherapy curative effect, remodeling the tumor microenvironment, promoting the anti-tumor immunity, enhancing the biomedical imaging and the like.

An anti-CTLA4 (cytotoxic T lymphocyte associated antigen 4) and anti-PD-1 (programmed cell death 1) bifunctional antibody. a pharmaceutical composition thereof and use thereof. Particularly, the anti-CLTA4 and anti-PD-1 bifunctional antibody comprises a first protein functional domain that targets PD-1 and a second protein functional domain that targets CTLA-4. The bifunctional antibody can bind to CTLA-4 and PD-1 specifically, relieve immunosuppression of CTLA4 and PD-1 on an organism specifically, activate T lymphocytes, and thus has good application prospects.

The invention discloses an application of ARN2966 in the treatment of UMOD (Urban Molecular Orthodontic Disease) gene mutant autosomal dominant hereditary renal tubular interstitial nephropathy (ADTKD), and belongs to the field of biomedicine. The ARN2966 has the advantages that the ARN2966 can be used for the treatment of UMOD gene mutant autosomal dominant hereditary ADTKD, and the ARN2966 can be used for the treatment of UMOD gene mutant autosomal dominant hereditary ADTKD; the application comprises the application of the amyloid precursor protein (APP)-CD74 signal axis blocking agent in the preparation of the medicine for treating the hereditary tubulointerstitial nephropathy, and the application comprises the application of the amyloid precursor protein (APP)-CD74 signal axis blocking agent in the preparation of the medicine for treating the hereditary tubulointerstitial nephropathy. Compared with the prior art, the key effect of an APP-CD74 signal axis in ADTKD-Umod pathogenesis is disclosed for the first time, and ARN2966 provides a brand new intervention strategy for treatment of ADTKD-Umod through targeted regulation and control of the pathway. Compared with a broad-spectrum anti-inflammatory drug, the ARN2966 has high targeting specificity, and side effects caused by non-specific immunosuppression can be avoided. Although the ARN2966 does not enter a clinical research stage at present, due to the unique action mechanism and verified safety characteristics of the ARN2966, the ARN2966 has remarkable transformation medical value and clinical application prospect in the aspect of developing ADTKD-Umod targeted therapeutic drugs.

The invention belongs to the field of biotechnology and medical technology, and discloses application of tumor-associated macrophages with high expression of SLC16A10 in prognosis diagnosis and treatment of colorectal cancer. According to the invention, colorectal cancer single-cell transcriptome sequencing data analysis before and after anti-PD-1 treatment is carried out in the earlier stage; the tumor-associated macrophage subgroup with high expression of the SLC16A10 is enriched in a response group after colorectal cancer anti-PD-1 treatment, and the prognosis of a colorectal cancer patient with high expression of the SLC16A10 is good. Knock-down of the SLC16A10 leads to reduction of expression of the macrophage M1 type marker, and activation and toxicity of co-cultured T cells are reduced. The SLC16A10 promotes T cell activation and weakens immunosuppression on T cells, so that colorectal cancer anti-PD-1 treatment response is caused. The research explains the influence and mechanism of the macrophage SLC16A10 on colorectal cancer anti-PD-1 treatment, and provides a new strategy and theoretical basis for immunotherapy of colorectal cancer.

The invention belongs to the field of biological medicine and ultrasonic medicine, and provides a barium titanate (BTO) piezoelectric material-based ultrasonic responsive targeting nano system (BTO at BAL), which is used for matrix microenvironment remodeling and immunopotentiation of compact tumors such as pancreatic cancer and the like. According to the nanoparticles, oleic acid modified BTO is taken as a core, ROS responsive prodrug molecules containing a small molecule PD-L1 inhibitor BMS1166 and a nitric oxide donor (Arg) 9 are loaded on the surface, and specific targeting on pancreatic cancer cells is realized by combining a targeting peptide LFC131. Under ultrasonic excitation, BTO generates reactive oxygen species (ROS), on one hand, (Arg) 9 is oxidized to release NO, tumor matrix is degraded, tumor hardness is reduced, drug delivery efficiency is improved, and meanwhile, ROS and NO synergistically enhance tumor immunogenicity; on the other hand, the ROS breaks a thioketal bond to release BMS1166, PD-L1 expression is down-regulated, and immunosuppression is reversed. According to the present invention, the significant tumor inhibition and immune activation effects are represented in the animal model, and the clinical transformation potential is provided.

The present application relates to a kind of pH / H2O2 dual-response drug-loaded hydrogel and its preparation method and application, by ε-polylysine derivative as antitumor active ingredient, with oxidized dextran through Schiff base reaction crosslinking rapid gelation. While using 2-formylphenyl boronic acid covalently package CD73 small molecule inhibitor APCP. ε-polylysine derivative has oncolytic activity, can induce ICD and promote the infiltration of immune cells in tumor cells. CD73 small molecule inhibitor APCP can block extracellular CD39-CD73-adenosine pathway, reduce the level of immunosuppressive metabolite adenosine in tumor tissue, so as to activate the infiltrated immune cells, restore its anti-tumor function. The hydrogel of ε-polylysine derivative and APCP co-delivery synergistically inhibits the effect of tumor growth, and its curative effect is greater than the treatment effect of single drug, and is superior to positive control drug oxaliplatin (OXA). The pH / H2O2 dual-response hydrogel is rapidly gelled, and has good biological safety under mild reaction conditions.

The invention discloses a core-shell microneedle for removing bacterial biofilms and a preparation method of the core-shell microneedle, and belongs to the technical field of biological medicines. The core-shell microneedle comprises a shell layer and a core layer, the shell layer comprises a shell layer material and copper peroxide nanoparticles loaded on the shell layer material, and the core layer comprises a core layer material and mesoporous polydopamine nanoparticles loaded on the core layer material, coated with citraconate and capable of targeting neutrophils. The biofilm can penetrate through a biofilm and preferentially release copper peroxide nanoparticles, the oxidation-reduction steady state in the biofilm is destroyed, bacteria are killed, and the biofilm is dispersed; the polypeptide can target neutrophil, relieve the immunosuppression state of congenital immune cells and recover the bacterial killing ability of the congenital immune cells, so that escaped bacteria are effectively phagocytized; through the synergistic effect of the two, the biological membrane can be completely removed, the biological membrane removing agent has a clinical application prospect, and bacterial drug resistance caused by long-term use of antibiotics is reduced.

The invention discloses a fusion protein taking peptide-N-glycosidase as an active component as well as a preparation method and application of the fusion protein, and belongs to the technical field of biological medicines. The fusion protein comprises: (a) peptide-N-glycosidase or a catalytically active fragment thereof; (b) an immunoglobulin Fc domain, or a combination of a tumor or immune cell antigen binding domain and an immunoglobulin Fc domain; (c) a linker peptide; wherein the form of the tumor or immune cell antigen binding domain is Fab, scFv or VHH; the peptide-N-glycosidase or the catalytic activity fragment of the peptide-N-glycosidase is connected with the Fc structural domain of the immunoglobulin through the connecting peptide; the immunoglobulin Fc domain mediates the fusion protein to form a homodimer or a heterodimer. According to the invention, the synergistic function of targeted binding and local deglycosylation of the target molecule is realized, so that the immunosuppressive activity of the target molecule is interfered, and the anti-tumor immune response is enhanced.

The invention discloses a key effect and a targeted intervention strategy of YTHDF1 in regulation and control of a hepatocellular carcinoma immunosuppression microenvironment. In the tumor-associated fibroblasts, YTHDF1 enhances the translation efficiency of OTUD5 mRNA through an m6A dependency mechanism, an up-regulated deubiquitination enzyme OTUD5 is directly combined with a tryptophan metabolic rate-limiting enzyme IDO1, ubiquitination degradation of the tryptophan metabolic rate-limiting enzyme IDO1 is inhibited, tryptophan is further driven to catabolism to generate kynurenine, regulatory T cell differentiation is promoted, and an immunosuppression microenvironment is formed. Spatial transcriptomics shows that YTHDF1 + CAFs and Tregs are significantly co-localized in tumor tissues and have metabolic interaction. Based on artificial intelligence virtual screening, it is found that a natural compound hesperidin can be specifically combined with a YTH structural domain of YTHDF1, an OTUD5-IDO1 signal axis mediated by the natural compound hesperidin is blocked, and the KYN level is remarkably reduced. Animal experiments prove that the tumor inhibition rate of combined treatment of hesperidin and anti-PD-1 is increased by 40% or above compared with that of a single drug group, and synergistic interaction is achieved by inhibiting Tregs infiltration and enhancing the activity of cytotoxic T lymphocytes.

The invention discloses an anti-tumor pharmaceutical composition based on NBDHEX and application of the anti-tumor pharmaceutical composition in treatment of immunosuppressive malignant tumors. The pharmaceutical composition comprises NBDHEX (6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol) and a PD-1 (programmed death-1) inhibitor, and is characterized in that the NBDHEX (6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol) and the PD-1 inhibitor are used as raw materials. The NBDHEX can induce tumor cells to generate immunogenic death and promote tumor antigen release, DAMPs signal activation and dendritic cell maturation, so that an immunosuppressive tumor microenvironment is remodeled, and CD8 + T cell infiltration and effector functions are enhanced. The pharmaceutical composition can significantly improve the anti-tumor immune response intensity and the treatment response rate. Animal experiments and cell experiments verify the synergistic anti-tumor effect of the composition in a lymphoma model. The immunosuppressive malignant tumors are suitable for treatment of various immunosuppressive malignant tumors including lymphoma, and are especially suitable for patients with poor single-drug reaction or drug resistance to immune checkpoint inhibitors, and a new way is provided for clinical treatment of tumors.

Embodiments of the present invention include methods of targeting acidosis (low pH) within the tumor microenvironment (TME) through the use of cathodic electrochemical reactions (CER). Low pH is oncogenic by supporting immunosuppression. Electrochemical reactions create local pH effects when a current passes through an electrolytic substrate such as biological tissue. Electrolysis has been used with electroporation (destabilization of the lipid bilayer via an applied electric potential) to increase cell death areas. However, the regulated increase of pH through only the cathode electrode has been ignored as a possible method to alleviate TME acidosis, which could provide substantial immunotherapeutic benefits. Here, ex vivo modeling shows that CERs can intentionally elevate pH to an anti-tumor level and that increased alkalinity promotes activation of naïve macrophages. Embodiments of the invention include pairing CER treatment protocols with existing electric field-based cancer therapies or use as a stand-alone therapy.