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Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.
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Humanos , Adenosina/farmacología , Linfocitos T , Inmunidad Adaptativa , Citocinas , Neoplasias/terapia , Microambiente TumoralRESUMEN
Objective:To develop and validate a nomogram model for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on preoperative enhanced computed tomography imaging features and clinical data.Methods:The clinical data of 210 patients with HCC undergoing surgery in the Second Affiliated Hospital of Anhui Medical University from May 2018 to May 2022 were retrospectively analyzed, including 172 males and 38 females, aged (59±10) years old. Patients were randomly divided into the training group ( n=147) and validation group ( n=63) by systematic sampling at a ratio of 7∶3. Preoperative enhanced computed tomography imaging features and clinical data of the patients were collected. Logistic regression was conducted to analyze the risk factors for HCC with MVI, and a nomogram model containing the risk factors was established and validated. The diagnostic efficacy of predicting MVI status in patients with HCC was assessed by receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) of the subjects in the training and validation groups. Results:The results of multifactorial analysis showed that alpha fetoprotein ≥400 μg/ml, intra-tumor necrosis, tumor length diameter ≥3 cm, unclear tumor border, and subfoci around the tumor were independent risk factors predicting MVI in HCC. A nomogram model was established based on the above factors, in which the area under the curve (AUC) of ROC were 0.866 (95% CI: 0.807-0.924) and 0.834 (95% CI: 0.729-0.939) in the training and validation groups, respectively. The DCA results showed that the predictive model thresholds when the net return is >0 ranging from 7% to 93% and 12% to 87% in the training and validation groups, respectively. The CIC results showed that the group of patients with predictive MVI by the nomogram model are highly matched with the group of patients with confirmed MVI. Conclusion:The nomogram model based on the imaging features and clinical data could predict the MVI in HCC patients prior to surgery.
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Objective Toexploretheimagingfeaturesofextramedullarydisease(EMD)in multiplemyeloma(MM).Methods Theclinicalandimagingdataof17patientswithpathologicallydiagnosedMMcombinedwithEMDwereanalyzedretrospectively.Results EMDhadcertainpredilectionsites,Centralnervoussysteminvasion (6):meningealinvasion (3:1 multiple,2focal),spinalcanal invasion (1focal),thelefttemporalpoleinvasion(1focal),theleftsideforeheadinvasion(1focal);Headandneckinvasion(3:allfocal);Thoraxinvasion(8):pleuralinvasion(6:5 multiple,1focal),intrapulmonaryinvasion(1focal),anteriormediastinalinvasion(1focal);Subcutaneoussofttissueinvasion(5:allmultiple);Muscleinvasion(2focal);Lymphnodeinvasion (1 multiple).BothCTand MRI showedsofttissuenodulesormasses.ThevaluesofCTwereabout30~70HU,especiallyin30~45HU,whileMRIpresentedequal orslightlylowsignalonT1WI,equalorslightlyhighsignalonT2WI,andhighsignalinthesequenceofDWIcombinedwithmoderate toobviousenhancement,Generally,theboundaryofEMDwereclearandtheshapeoftheselesionswereregular,However,theinvasion tomuscleinsomelesionsshowedthepatternofinvasivegrowth.Conclusion EMDofmultiplemyelomamayhappenanywhere,and thepleural,meningesandsubcutaneoussofttissuesarethemostcommonlocation.CTandMRIcanshowtheEMDverywell.Thelocation, size,shapeandrelationshipwithsurroundingtissuesoftheselesionshavecertainreferencevaluesforthediagnosisanddifferential diagnosisofEMD.
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Objective To investigate the CT features of clear cell renal carcinoma (ccRCC)and angiomyolipoma with minimal fat (AMLmf)and to improve the CT diagnostic accuracy of these two diseases.Methods The CT features of 55 patients with pathologically-confirmed ccRCC and 1 2 patients with pathologically-confirmed AMLmf were analyzed retrospectively,including the CT value in both plain and tri-phase enhanced CT scan,tumor enhancement rate(△R1,△R2,△R3),maximum diameter,enhanced homogeneity,location of the main tumor,cortex raising signs,etc.The statistical analysis was carried on.Results The maximum diameter,the CT value in parenchymal phase,enhancement rate (△R1,△R2,△R3)of tumors in ccRCC group were significantly higher than those of tumors in AMLmf group,and the CT value in plain CT scan in ccRCC group was significantly lower than that in AMLmf group (all P<0.05).No statistically significant difference was found in the CT value of the tumor in corticomedullary phase and in excretion phase (both P>0.05).The rate of extrarenally-located main tumors of AMLmf group was significantly higher than that of ccRCC group (P=0.020),the location of main tumors and cortex raising signs showed no statistically significant difference with the maximum tumor diameter(both P>0.05).The enhanced homogeneity of the tumor in corticomedullary phase,parenchymal phase and excretion phase in ccRCC group was lower than that in AMLmf group (all P<0.05).Conclusion The CT value in plain CT scan in ccRCC group is lower than that in AMLmf group;the enhancement rate of the ccRCC group is higher than that of the AMLmf group;the enhanced homogeneity of the ccRCC group is worse than that of the AMLmf group.The extrarenally-located main tumors are more commonly seen in AMLmf than in ccRCC,and the cortex raising signs and the location of main tumors are unrelated to the size of the tumor.
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Objective To investigate the clinical feasibility of contrast?enhanced three dimensional T2WI turbo?spin?echo sequence with short?term inversion recovery and sampling perfection using different flip angle evolutions (3D STIR T2WI SPACE) sequence in the brachial plexus neurography. Methods Thirty two patients were prospectively chosen and performed with brachial plexus plain scanning on a 3.0 T MR scanner by using plain and contrast?enhanced 3D STIR T2WI SPACE sequence. Thirteen of them underwent plain scan, 9 of them underwent contrast?enhanced scan, and 10 of them underwent both plain scan and enhanced scan. The visibility of the brachial plexus were scored and contrast to noise ratio (CNR) were measured by two experienced radiologists. The results between plain and contrast?enhanced imaging were compared by t test. The 10 subjects received both enhance and plain imaging, were performed with paired t test. Results In 32 patients, the visibility score of brachial plexus nerve and CNR were 7.8 ± 1.3 and 24.97±3.41 in the plain scan group, and 13.1±1.7 and 38.49±4.95 in enhanced scan group, respectively. There were statistically significant differences in the two groups(t=-11.72,P<0.01;t=-10.47, P<0.01). In 10 cases with plain and enhanced brachial plexus imaging, the average score of the brachial plexus were 7.4 ± 1.7 and 13.3 ± 1.6, the average CNR were 26.23 ± 4.43 and 38.19 ± 5.03 respectively. There were statistically significant differences (t=- 8.22, P<0.01; t=- 5.64,P<0.01). The score results were analyzed for consistency. Plain images Kappa value was 0.684, which shows moderate consistency and enhanced images Kappa value= 0.822, which shows excelent consistency. Conclusions The contrast?enhanced 3D STIR T2WI SPACE sequences may suppress background tissue signals, which is helpful to display brachial plexus, therefore it is of important value for the early diagnosis of brachial plexus neuropathy.
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Purpose The main purposes of our research were to: 1. set up the method of the RGDHirudin microsphere preparation; 2. set up the method to test the activity and the content of the medicine contained in the microsphere; 3. analyse the key factors on the quality of the microsphere preparation. Methods Co-poly lactic acid glycolic acid (PLGA) microsphere was prepared by a modified solvent evaporation method by a double emulsion with the use of polyvinylalcohol (PVA) as emulsification; PLGA was used as biodegradable material and dichloromethane as organic solvent. The influence of formulation factors including the W1/O on microsphere diameter distribution and yield coefficient;PVA concentration on microsphere appearance, encapsulation and yield coefficient; ultrasound on spherulization average and medicine activity; stirring speed on spherulization average and microsphere appearance; PLGA on microsphere appearance and microsphere dispersity; concentration of NaCl on encapsulation efficiency, yield coefficient and medicine content etc were studied. Results The size of all the fabricated microsphere was measured according to the several factors that affect the particle size. The average diameter was 81.38 μm, which is good for further research. The medicine content and the percent yield of all the microsphere was high, which ranged from 83. 92% - 96. 3% and 79.93% - 95.05% respectively. The encapsulation efficiency was about 23.95% - 65. 13%. We found that the concentration of the NaCl and PVA were the very important factors to the encapsulation efficiency. Physiological activity of RGD-Hirudin containing in the microsphere and the release rate of the microsphere were controlled. Furthermore, the release rate was stable. Conclusions The physiologic activity of RGD-Hirudin released from the microspheres was stable. PLGA-RGD-Hirudin microspheres were controlled released by the in vitro studies. Therefore, the in vivo experiment was well grounded.
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Objective To evaluate the effect on the development of hip joint by gluteal muscle contracture and to study the significance of early surgical treatment for this disease.Methods X-ray films of pelvis in 102 cases with gluteal muscle contracture were taken before surgical treatment.The acetabular index,the neck-shaft angle and the acetabular-head index(AHI) were measured.Results The neck shaft angle(x=149.64) and the CE angle(x=34.12) were increased,the acetabular-head index(x=72.3%) was decreased,and the acetabulainr index(x=13.6) was normal.Conclusion The gluteal muscle contracture can causes coxa valga and subluxation of the hip joint,early surgical treatment is needed.
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Objective To evaluate the imaging findings of the annular pancreas in newborn and the diagnostic value.Methods Clinical data,X-ray and CT features of annular pancreas in 7 cases of newborn were retrospectively analyzed,and 6 cases were confirmed by operations.Results Abdominal erect position plain films were performed in six patients and showed typical "double bubble sign" without distal gas in 5 cases,with a little gas in 1 case.Seven patients underwent upper gastrointestinal contrast studies and showed stenosis of the descending duodenum like "the thin striation",and contrast agent passed with difficulty.There were soft tissue shadows encircling the descending duodenum in 4 cases on CT plain scans,in which 3 cases showed stenosis of the descending duodenum like "the mouse tail",and the soft tissue shadows obviously enhanced the same as enhanced pancreas on contrast-enhanced CT scans.Conclusion The annular pancreas in newborn are of characteristics at imageology.
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Ultrastructural localization of alkaline phosphatase (AKP) was observed with histochemical method in 10 cases of endometrium. AKP was localized on plasma membranes of glandular cells in normal proliferative and adenomatous hyperplastic endometrium. Uhrastractural、locatization of AKP has no significant change in endometrial cancer. In differentiated endometrial cancer AKP was predominantly localized on microvilli and apical plasma membranes of tumor cells which were adjacent to glandular cavity; and in undifferentiated cancer AKP was evenly distributed on plasma membaanes of tumor cells.