Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer

BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment

In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

Tumor infiltrating lymphocytes in gastric cancer:Unraveling complex interactions for precision medicine

This editorial will focus on tumor immunity and the factors that alter the tumor immune micro-environment.The role of tumor infiltrating lymphocytes(TILs)will also be discussed in detail,including the types,mechanism of action,and role.Gastric cancer(GC)often presents in the advanced stage and has various factors predicting the outcomes.The interplay of these factors and their correlation with the TILs is discussed.A literature review revealed high intratumoral TILs associated with higher grade,HER2-,and Helicobacter pylori negativity.Moreover,stromal(ST)TILs correlated with lower grade and lesser recurrence risk in GC.High TILs in ST and invasive border also correlated with mismatch repair deficiency status.Further characterization of the CD3+,CD8+,and other cells is also warranted.In the future,this complex correlation of cancer cells with the immune system can be explored for therapeutic avenues.

IQGAP3 promotes the progression of glioma as an immune and prognostic marker

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

Evaluating tumor-infiltrating lymphocytes in hepatocellular carcinoma using hematoxylin and eosin-stained tumor sections

BACKGROUND Tumor-infiltrating lymphocytes(TILs)constitute a prognostic factor in hepatocellular carcinoma(HCC).However,different methods of assessing TILs have various pre-analytical,analytical,and post-analytical challenges.The evaluation of TILs in hematoxylin and eosin(H&E)-stained tumor sections proposed by the International Immuno-Oncology Biomarker Working Group was demonstrated to be a reproducible,affordable and easily applied method in many tumors.AIM To evaluate the prognostic significance of TILs in H&E-stained slides of HCCs.METHODS This was a retrospective study performed in the hospital.HCC patients who underwent liver resection between 2015 and 2017 in Zhongshan Hospital were enrolled in this study.Patients who experienced recurrence or received therapy in addition to antiviral therapy before surgery at this time were excluded.A total of 204 patients were enrolled in the study.The ILs were counted manually in tumor sections stained with H&E under an optical microscope at 400×.The ILs were assessed separately in the center of the tumor(TILs^(CT)),the invasive front(TILs^(IF)),and peritumor(PILs)areas.Univariate and multivariate survival analyses were performed using a Cox regression model.P<0.05 was considered statistically significant and all P-values were two-sided.RESULTS Among the 204 patients,univariate analysis indicated that macrovascular invasion(MaVI)(P=0.001),microvascular invasion(MVI)(P=0.012),multiple tumors(P=0.008),large tumors(>10 cm)(P=0.001),absence of a tumor capsule(P=0.026),macrotrabecular histological subtype(P=0.001),low density of TILs^(CT)(P=0.039),TILs^(IF)(P=0.014),and PILs(P=0.010)were predictors of progressionfree survival(PFS).Cox multivariate analysis indicated that MaVI(P=0.009),absence of a tumor capsule(P=0.031),low-density of TILs^(IF)(P=0.047)and PILs(P=0.0495)were independent predictors of PFS.A three-category analysis was carried out by combining TILs^(CT),TILs^(IF),and PILs,after which HCCs were classified into immune^(high)[(TILs^(CT))^(high),(TILs^(IF))^(high),and PILs^(high),83 cases],immune^(mod)(tumors other than immune^(high) and immune^(low) subtypes,94 cases),and immune^(low)[(TILs^(CT))^(low),(TILs^(IF))^(low),and PILs^(low),27 cases]subtypes.The immune^(high) subtype had a lower rate of MVI(40.96%)than the immune^(mod)(61.70%,P=0.017)and immune^(low)(66.67%,P=0.020)subtypes.The recurrence rates of the immune^(high),immune^(mod) and immune^(low) subtypes were 10.8%,25.5%and 33.3%,respectively.CONCLUSION HCC patients with high infiltrating lymphocytes tend to have a lower recurrence rate and less MVI.The evaluation of TILs in H&E-stained specimens could be a prognostic parameter for HCC.

Invasive front of colorectal cancer:Dynamic interface of pro-/anti-tumor factors

Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carci-noma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of "tumor budding" ,a feature which can be highly specific for tumors showing an inf iltrating tumor growth pattern. Importantly,tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact,several tumor-associated antigens such as CD3,CD4,CD8,CD20,Granzyme B,FOXP3 and other immunological or inflammatory cell types have been identified as poten-tially prognostic in patients with this disease. Evidence seems to suggest that the balance between protumor (including budding and inf iltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand,the inf iltrating tumor border configuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other,the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features,such as the BRE and Gleason scores,the ratio of pro-and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis staging to improve the clinical management of patients with this disease.

Morphological observation of tumor infiltrating immunocytes in human rectal cancer

AIM： To investigate the morphological characterization of tumor infiltrating dendritic cells （TIDCs） and tumor infiltrating lymphocytes （TILs） in human rectal cancer. METHODS： Light and electron microscopy as well as immunohistochemistry were used to observe the distributive and morphological changes of TIDCs and TILs. RESULTS： TIDCs were mainly located in tumor-surrounding tissue. The number of TIDCs in the earlier stage was higher than that in the later stage （P〈 0.01）. TILs were mainly seen in adjacent tissue of cancers and tumor-surrounding tissue. There were more TILs in the earlier stage than that in the later stage （P〈0.01）. Under electron microscope, TIDCs were irregular in shape and exhibited many dendritic protrusions. It isn＇t obvious that cancer cells perforated the basement membrane and TILs were arranged along the basement membrane in the earlier stage. In the later stage, it is explicit that cancer cells perforated the basement membrane and surrounded by TILs. There were contacts among TIDCs, TILs and tumor cell. One IIDCs contacted one or several TILs which clustered around TIDCs. Glycogen granules were seen between TIDCs and Tits. CONCLUSION： The number of TIDCs and TILs is related with tumor progression There exist close relationships among TIDCs, TILs and tumor cell.

EXPRESSION AND SIGNIFICANCE OF TUMOR INFILTRATING DENDRITIC CELLS IN RENAL CELL CARCINOMA

Objective: To study the expression of dendritic cells in human renal cell carcinoma and explore the cause, so to reveal the mechanism of escaping immune surveillance in RCC. Methods: The expressions of CD83+DCS, CD1a+DCS,VEGF and TGF-β1 in tumoral, peritumoral and normal kidney tissues of RCC in 30 cases were detected by immunohistochemistry using streptavidin/peroxidese(SP) Results: CD83+DCS were mainly located in the peritumoral areas; whereas CD1a+DCS、were mainly retained within the cancer nests. The number of CD83+DCS was inversely correlated with the clinical stage(P<0.05); but there were no significant correlations between the number of CD1a+DCS、and the clinical stage(P>0.05). The expressions of CD83+DCS and CD1a+DCS have significant difference between the tumoral, peritumoral and normal kidney tissues(P<0.001). The expression of VEGF and TGF-β1 were significantly lower in samples with highly infiltrating CD83+DCS(P<0.05); Whereas CD1a+DCS were not (P>0.05). Conclusion: DC has the tendency to gathering in tumor, but because of the immunosuppressive cytokins, for example VEGF and TGF-β1, inhibits the maturation of DC, there are less mature TIDCS(CD83+TIDCS) in the tumoral tissues, they are mainly located in the peritumoral areas. This may contribute to the mechanism of escaping immune surveillance in RCC.

Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma:Relation to the immune cycle

BACKGROUND Various histological types of gastric carcinomas(GCs)differ in terms of their pathogenesis and their preexisting background,both of which could impact the tumor immune microenvironment(TIME).However,the current understanding of the immune contexture of GC is far from complete.AIM To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle concept.METHODS In total,50 GC cases were examined(15 cases of diffuse GC,31 patients with intestinal-type GC and 4 cases of mucinous GC).The immunophenotype of GC was assessed and classified as immune desert(ID),immune excluded(IE)or inflamed(Inf)according to CD8+cell count and spatial pattern.In addition,CD68+and CD163+macrophages and programmed death-ligand 1(PD-L1)expression were estimated.RESULTS We found that GCs with different histological differentiation demonstrated distinct immune contexture.Most intestinal-type GCs had inflamed TIMEs rich in both CD8+cells and macrophages.In contrast,more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+lymphocytes but abundant CD68+macrophages,while mucinous GC had an IE-TIME with a prevalence of CD68+macrophages and CD8+lymphocytes in the peritumor stroma.PD-L1 expression prevailed mostly in intestinal-type Inf-GC,with numerous CD163+cells observed.Therefore,GCs of different histological patterns have specific mechanisms of immune escape.While intestinal-type GC was more often related to PD-L1 expression,diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters.CONCLUSION These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.

TREATMENT OF 23 PATIENTS WITH ADVANCED GASTRIC CANCER BY INTRAVENOUSLY TRANSFER OF AUTOLOGOUS TUMOR-INFILTRATING LYMPHOCYTES COMBINED WITH rIL-2

Tumor-infiltrating lymphocytes (TIL)isolated from metastatic lymph nodes in patients with nonoperable advanced gastric cancer were induced to become LAK-like cytotoxic activrty of TIL after in vitro culture with rlL-2.Twenty-three patients with advanced gastric cancer were treated by intravenously transfer of autologous TIL combined with rlL-2. The tumor forus disappeared (complete remission, CR) in 3 patients (13. 0%) and significantly decreased (partial remission, PR) in 5 patients (21. 7%). Fifteen patients did not respond to the treatment. The amount of soluable IL-2 receptor in serum was significantly decreased after treatment, the cytotoxicity of NK cells and OT test were significantly increased. No significant difference in CD4/CD8 was found between before and after treatment. No serious side effect was obseved in the treatment.

Effect of Tumor Infiltrating Lymphocyte on Local Control of Rectal Cancer after Preoperative Radiotherapy

Objective： To study the effect of tumor infiltrating lymphocytes at cancer nest on local control of rectal cancer after preoperative radiotherapy. Methods： From Jan. 1999 to Oct. 2007, a total of 107 patients with rectal cancer were reviewed. They were treated by preoperative radiotherapy, 30 Gy/10 fractions/12 days. Two weeks later, the patient underwent a surgical operation. Their pathological samples were kept in our hospital before and after radiotherapy. Lymphocyte infiltration （LI） degree, pathologic degradation and fibrosis degree after radiotherapy in paraffin section were evaluated under microscope. Results： After followed-up of 21 months （2-86 months）, a total of 107 patients were reviewed. Univariate analysis showed that lymphocyte infiltration （LI）, fibrosis and pathologic changes after radiotherapy were significant factors on local control. Logistic regression analysis showed that LI after radiotherapy was a significant effect factor on local control. Conclusion： LI, fibrosis and pathologic degradation after radiotherapy are significant for local control of rectal cancer after preoperative radiotherapy. LI after radiotherapy was a significantly prognostic index for local control of rectal cancer after preoperative radiotherapy.

PREPARATION AND CYTOLYTIC TUMOR ACTIVITY OF OSTEOSARCOMA TUMOR INFILTRATING LYMPHOCYTES IN VITRO

In this study, the isolation, purification and differentiation of tumor-lnflltratlng lymphocytes (TIL) from 6 fresh osteosarcoma specimens were achieved by discontinuous density gradient centrifugation. One specimen of the osteosarcoma TIL were enlarged in IL-2 for long time in vitro, reaching 28 days and their cytolytic activity against different tumor cell lines was Investigated. The experimental results indicated that the preparation of osteosarcoma TIL adopted by the mechanical means was simple, having higher purifity, keeping higher effects on killing NK- sensitive tumor cell lines and NK-insensitive tumor cell lines as well as rapid proliferation in vitro cultured in IL-2.

Prognostic significance of serum inflammation indices for different tumor infiltrative pattern types of gastric cancer

BACKGROUND Inflammatory indices are considered to be potential prognostic biomarkers for patients with gastric cancer(GC).However,there is no evidence defining the prognostic significance of inflammatory indices for GC with different tumor infiltrative pattern(INF)types.AIM To evaluate the significance of inflammatory indices and INF types in predicting the prognosis of patients with GC.METHODS A total of 962 patients who underwent radical gastrectomy were retrospectively selected for this study.Patients were categorized into the expansive growth type(INFa),the intermediate type(INFb),and the infiltrative growth type(INFc)groups.The cutoff values of inflammatory indices were analyzed by receiver operating characteristic curves.The Kaplan–Meier method and log-rank test were used to analyze overall survival(OS).The chi-square test was used to analyze the association between inflammatory indices and clinical characteristics.The independent risk factors for prognosis in each group were analyzed by univariate and multivariate analyses based on logistic regression.Nomogram models were constructed by R studio.RESULTS The INFc group had the worst OS(P<0.001).The systemic immune-inflammation index(P=0.039)and metastatic lymph node ratio(mLNR)(P=0.003)were independent risk factors for prognosis in the INFa group.The platelet-lymphocyte ratio(PLR)(P=0.018),age(P=0.026),body mass index(P=0.003),and postsurgical tumor node metastasis(pTNM)stage(P<0.001)were independent risk factors for prognosis in the INFb group.The PLR(P=0.021),pTNM stage(P=0.028),age(P=0.021),and mLNR(P=0.002)were independent risk factors for prognosis in the INFc group.The area under the curve of the nomogram model for predicting 5-year survival in the INFa group,INFb group,and INFc group was 0.787,0.823,and 0.781,respectively.CONCLUSION The outcome of different INF types GC patients could be assessed by nomograms based on different inflammatory indices and clinicopathologic features.

ISOLATION AND CULTURE OF TUMOR-INFILTRATING LYMPHOCYTES FROM MOUSE HEPATOMA

By uaing enzyme digestion and Flcoll- Hypaque or Percoll discontinuous density methods, we have successfully obtained tumor-infiltrating lymphocytes (TIL) from mouse hepatoma. When analyzing the purity of TIL after separation. It was found that Percoll was more effective than Flcoll (P<0. 01). TIL could be activated In the presence of recombinant lL-2 (rIL-2) and begin to expand after culturing for 5-7 days, the tumor cells tend to decrease and disappeared after 14 days or so. TIL increased 105-fold over 40 days. Conditioned medium containing supernatant of PHA and rIL- 2 stimulated syngeneic spleen cell culture could promote the expansion of TIL.

The Tumor Infiltrating Lymphocytes (TILs): Did We Find the Missed Piece of the Huge Puzzle?

Tumor infiltrating lymphocytes (TILs) are used in evaluating the prognosis and determining treatment of different types of cancer with variable degrees of success. The usage of checkpoint inhibitor immunotherapy as a treatment variety for cancer and Adoptive cell therapy is associated with many complications, severe side effects and high expenses. Recently, in a limited number of metastatic GIT and breast cancers, the identification of T-cell specific against so-called tumor neo-antigens and Adoptive transfer of those lymphocytes resulted in some improvement. In 2020, Detection of a T cell receptor (TCR) in a T cell clone that recognized and killed most human cancer cell lines in vitro via the monomorphic MHC class I-related protein MR1, offers an opportunity for pan-cancer therapy Twenty three years earlier, Moist Heat was used successfully to activate a whole different and new immune response that was able to detect genetic mutation in the affected cancer cells and cured many cases of squamous and basal cell carcinomas. In this commentary review, we aimed to revise the literature for updates of TILs usage in cancer prognosis and treatment.

Correlations between P2RX1 Expression and Gastrointestinal Cancers Prognosis and Immune Infiltration Based on Bioinformatics Analysis

This study was conducted to explore the correlations between the expression,methylation,and various clinicopathological factors of purinergic P2X1 receptor(P2RX1)and the prognosis of patients with gastrointestinal tumors.The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of P2RX1 in different types of gastrointestinal cancers.Kaplan-Meier analysis and univariate Cox regression analysis were used to analyze the correlations between P2RX1 expression and the prognosis of various gastrointestinal tumors.Correlations between P2RX1 expression and N6 methyladenine(m6A)-related genes as well as immune checkpoint genes were analyzed by R packages(R version:4.0.3)based on TCGA database.The association between P2RX1 methylation level and the prognosis of patients with gastrointestinal cancers was analyzed using the MethSurv database.In order to explore the biological functions of P2RX1 in hepatocellular carcinoma,the Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analysis were carried out using R software.In order to evaluate the correlations between P2RX1 and tumor immune infiltration,Spearman correlation test was performed.The correlations between P2RX1 expression and immune score as well as immune checkpoint genes were analyzed based on TCGA and Tumor Immune Estimation Resource(TIMER)databases.The expression of P2RX1 was found to be significantly downregulated in gastrointestinal tumors except in cholangiocarcinoma(P<0.05).High expression of P2RX1 tended to present better prognosis in hepatocellular carcinoma(P<0.05).It was noted that cg06475633 of P2RX1 presented a higher methylation level compared with other CpG sites in hepatocellular carcinoma.Overall,six CpGs of P2RX1 were associated with significant prognosis in patients with hepatocellular carcinoma(P<0.05).Among all the 20 m6A-related genes,Wilms'tumor 1-associating protein(WTAP)was the most strongly correlated with P2RX1 in hepatocellular carcinoma.Gene enrichment analysis showed that P2RX1 is widely involved in the proliferation,activation,organization,and differentiation of various immune cells.After investigating the TIMER database,P2RX1 was found to be tightly correlated with immune infiltrating cells in gastrointestinal tumors,especially with dendritic cells.Moreover,P2RX1 was found to be strongly positively associated with programmed cell death 1(PD1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated protein 4(CTLA4)in hepatocellular carcinoma(P<0.05).In conclusion,the dual role of P2RX1 in cancers and its involvement in the recruitment as well as regulation of tumor infiltrating cells in gastrointestinal cancers may be appreciated through this study.

Immunogenic cell death-related long noncoding RNA influences immunotherapy against lung adenocarcinoma

Lung adenocarcinoma(LUAD)is the leading cause of cancer-related deaths,accounting for over a million deaths worldwide annually.Immunogenic cell death(ICD)elicits an adaptive immune response.However,the role of ICD-related long noncoding RNAs(lncRNAs)in LUAD is unknown.In this study,we investigated the characteristics of the tumor microenvironment in LUAD,the prognostic significance of ICD-related lncRNAs,and the half-maximal inhibitory concentration(IC50)of possible chemotherapeutic drugs.We sorted prognostic lncRNAs using univariate Cox regression and constructed a risk signature based on them.We then confirmed the model’s accuracy and generated a nomogram.Additionally,we performed immune microenvironment analysis,somatic mutation calculation,Tumor Immune Dysfunction and Exclusion(TIDE)analysis,and anticancer pharmaceutical IC50 prediction.Least absolute shrinkage and selection operator Cox regression identified 27 prognostic lncRNAs related to ICD,and a unique risk signature using 10 ICD-related lncRNAs was constructed.The risk score was confirmed to be a reliable predictor of survival,with the highest c-index score.The signature had a remarkable predictive performance with clinical applicability and could accurately predict the overall survival in LUAD.Furthermore,the lncRNA signature was closely associated with immunocyte invasion.We also analyzed the correlation between the risk score,tumor-infiltrating immune cells,and prognosis and identified high immune and ESTIMATE scores in low-risk patients.Moreover,we observed elevated checkpoint gene expression and low TIDE scores in high-risk patients,indicating a good immunotherapy response.Finally,high-risk patients were shown to be susceptible to anticancer medications.Therefore,our unique risk signature comprising 10 ICD-related lncRNAs was demonstrated to indicate the characteristics of the tumor-immune microenvironment in LUAD,predict patients’overall survival,and guide individualized treatment.

Right hemicolectomy combined with duodenum-jejunum Roux-en-Y anastomosis for hepatic colon carcinoma invading the duodenum:A single-center case series

BACKGROUND Hepatic colon carcinoma invading the duodenum is not common in clinical practice.Surgical treatment of colonic hepatic cancer that invades the duodenum is difficult,and the surgical risk is high.AIM To discuss the efficacy and safety of duodenum-jejunum Roux-en-Y anastomosis for the treatment of hepatic colon carcinoma invading the duodenum.METHODS From 2016 to 2020,11 patients from Panzhihua Central Hospital diagnosed with hepatic colon carcinoma were enrolled in this study.Clinical and therapeutic effects and prognostic indicators were retrospectively analyzed to determine the efficacy and safety of our surgical procedures.All patients underwent radical resection of right colon cancer combined with duodenum-jejunum Roux-en-Y anastomosis.RESULTS The median tumor size was 65 mm(r50-90).Major complications(ClavienDindoI-II)occurred in 3 patients(27.3%);the average length of hospital stay was 18.09±4.21 d;and only 1 patient(9.1%)was readmitted during the 1st mo after the surgery.The 30-d mortality rate was 0%.After a median follow-up of 41 m(r7-58),the disease-free survival at 1,2,and 3 years was 90.9%,90.9%and 75.8%,respectively;the overall survival at 1,2,and 3 years was 90.9%.CONCLUSION In selected patients,radical resection of right colon cancer combined with duodenum-jejunum Roux-en-Y anastomosis is clinically effective,and the complications are manageable.The surgical procedure also has an acceptable morbidity rate and mid-term survival.

Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration

Objective:Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer;however,its exact molecular mechanisms in this process remain unclear.This study explores how aconite aqueous extract(AAE)inhibits hepatocellular carcinoma(HCC).Methods:An in vivo mouse model of subcutaneous liver cancer was established.After AAE treatment,immunohistochemistry(IHC)was used to determine the effect of AAE on natural killer(NK)cells.Subsequently,C57BL/6 mice were used to establish the subcutaneous tumor model,and a group of these mice were treated with anti-PK163 antibody to remove NK cells,which was verified by flow cytometry and IHC.The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8.The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay.The effect of AAE on the migration of NK cells was determined using a transwell assay.Finally,the molecular mechanism was investigated using the Western blotting method.Results:We demonstrated that the ability of AAE to induce overexpression of the cytokine C–C motif chemokine ligand 2(CCL2)in HCC cells is fundamental to the infiltration of NK cells into the tumor bed.Mechanistically,we found that the upregulation of CCL2 was achieved by the activation of c-Jun Nterminal kinase but not extracellular regulated protein kinase or p38.Conclusion:Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors,which could help to improve the efficacy of HCC treatments.

Heparanase expression,degradation of basement membrane and low degree of infi ltration by immunocytes correlate with invasion and progression of human gastric cancer

AIM： To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients. METHODS： The heparanase expression, continuity of basement, degree of infiltration by dendritic cells and lymphocytes in gastric cancer tissues from 33 the early and late stage patients were examined by immunohistochemistry, in situ hybridization and transmission electron microscopy. RESULTS： Heparanase mRNA expression in the late stage patients with gastric cancer was stronger than that in the early stage gastric cancer patients. In the early stage gastric cancer tissues, basement membrane （BM） appeared intact, whereas in the late stage, discontinuous BM was often present. The density of Sl00 protein positive tumor infiltrating dendritic cells （TIDC） in the early stage gastric cancer tissues was higher than that in the late stage. The infiltrating degree of tumor infiltrating lymphocytes （TIL） in the early stage patients whose tumor tissues contained a high density of TIDC was significantly higher than that in the late stage gastric cancer tissues patients with a low density of TIDC. There were few cancer cells penetrated through the continuous BM of cancer nests in the early stage gastric cancers, but many cancer cells were found outside of the defective BM of cancer nests in the late stage. CONCLUSION： Our results suggest that strongheparanase expression is related with the degradation of BM which allows or accelerates tumor invasion and metastasis. However, high density of TIDC and degree of infiltration by TIL are associated with tumor progression in human gastric cancers.