Pathology oncology research : POR最新文献

{"title":"EGFR T790M Mutation Detection in Patients With Non-Small Cell Lung Cancer After First Line EGFR TKI Therapy: Summary of Results in a Three-Year Period and a Comparison of Commercially Available Detection Kits.","authors":"Eszter Bencze, Krisztina Bogos, Andrea Kohánka, László Báthory-Fülöp, Veronika Sárosi, Erzsébet Csernák, Nóra Bittner, Zsombor Melegh, Erika Tóth","doi":"10.3389/pore.2022.1610607","DOIUrl":"https://doi.org/10.3389/pore.2022.1610607","url":null,"abstract":"EGFR mutation in non-small cell lung cancer (NSCLC) offers a potential therapeutic target for tyrosine kinase inhibitor (TKI) therapy. The majority of these cases, however eventually develop therapy resistance, mainly by acquiring EGFR T790M mutation. Recently, third-generation TKIs have been introduced to overcome T790M mutation-related resistance. Cell free circulating tumor DNA (liquid biopsy) has emerged as a valuable alternative method for T790M mutation detection during patient follow up, when a tissue biopsy cannot be obtained for analysis. In this study, we summarized our experience with Super-ARMS EGFR Mutation Detection Kit (AmoyDx) on 401 samples of 242 NSCLC patients in a 3-year period in Hungary, comprising 364 plasma and 37 non-plasma samples. We also compared the performance of two commercially available detection kits, the cobas EGFR Mutation test v2 (Roche) and the Super-ARMS EGFR Mutation Detection Kit (AmoyDx). The same activating EGFR mutation was detected with the AmoyDx kit as in the primary tumor in 45.6% of the samples. T790M mutation was identified in 48.1% of the samples containing activating EGFR mutation. The detection rate of T790M mutation was not dependent on the DNA concentration of the plasma sample and there was no considerable improvement in mutation detection rate after a second, subsequent plasma sample. The concordance of EGFR activating mutation detection was 89% between the two methods, while this was 93% for T790M mutation detection. The AmoyDx kit, however showed an overall higher detection rate of T790M mutation compared to the cobas kit (p = 0.014). T790M mutation was detected at 29.8% of the patients if only plasma samples were available for analysis, while the detection rate was 70.2% in non-plasma samples. If the activating EGFR was detected in the plasma samples, the detection rate of T790M mutation was 42.4%. Although non-plasma samples provided a superior T790M mutation detection rate, we found that liquid biopsy can offer a valuable tool for T790M mutation detection, when a tissue biopsy is not available. Alternatively, a liquid biopsy can be used as a screening test, when re-biopsy should be considered in case of wild-type results.","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610607"},"PeriodicalIF":2.8,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9579289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40655546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients-Real-World Data From Hungary.","authors":"Szilvia Lovas,&nbsp;Nóra Obajed Al-Ali,&nbsp;Gergely Varga,&nbsp;Virág Szita,&nbsp;Hussain Alizadeh,&nbsp;Márk Plander,&nbsp;Péter Rajnics,&nbsp;Árpád Illés,&nbsp;Zsuzsa Szemlaky,&nbsp;Gábor Mikala,&nbsp;László Váróczy","doi":"10.3389/pore.2022.1610645","DOIUrl":"https://doi.org/10.3389/pore.2022.1610645","url":null,"abstract":"<p><p>Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (<i>p</i> = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS<i>.</i> PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610645"},"PeriodicalIF":2.8,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9573944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40656680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On-Target Side Effects of Targeted Therapeutics of Cancer.","authors":"József Tímár,&nbsp;Andrea Uhlyarik","doi":"10.3389/pore.2022.1610694","DOIUrl":"https://doi.org/10.3389/pore.2022.1610694","url":null,"abstract":"<p><p>The concept of precision medicine is based on the identification of hallmarks of cancer to exploit them as drug targets. The basic idea was that in this way the therapeutic modalities will be more effective and the side effects will be less. Since the majority of these novel modalities are not specific for a cancer-related biological process or a cancer-specific (mutant) target protein, it is not a surprise that we had to learn new type of side effects, because these therapeutics also affect physiological or pathological processes. Even more, in cases of some of these novel therapies we were able to discover new molecular mechanisms of physiological and pathological processes. Identification of the on-target side effects of targeted drugs can help to prevent the development of them or better manage the patients when emerge during cancer therapy.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610694"},"PeriodicalIF":2.8,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33496008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing a Phenotypical Appearance of Ibrutinib Resistance in Patients With Chronic Lymphocytic Leukaemia by Flow Cytometry.","authors":"Ferenc Takács,&nbsp;Lili Kotmayer,&nbsp;Ágnes Czeti,&nbsp;Gábor Szalóki,&nbsp;Tamás László,&nbsp;Gábor Mikala,&nbsp;Ágnes Márk,&nbsp;András Masszi,&nbsp;Péter Farkas,&nbsp;Márk Plander,&nbsp;Júlia Weisinger,&nbsp;Judit Demeter,&nbsp;Sándor Fekete,&nbsp;László Szerafin,&nbsp;Beáta Margit Deák,&nbsp;Erika Szaleczky,&nbsp;Adrienn Sulák,&nbsp;Zita Borbényi,&nbsp;Gábor Barna","doi":"10.3389/pore.2022.1610659","DOIUrl":"https://doi.org/10.3389/pore.2022.1610659","url":null,"abstract":"<p><p><b>Background:</b> Ibrutinib is widely known as an effective and well-tolerated therapeutical choice of the chronic lymphocytic leukaemia (CLL). However, acquired resistance may occur during the treatment, causing relapse. Early detection of ibrutinib resistance is an important issue, therefore we aimed to find phenotypic markers on CLL cells the expression of which may correlate with the appearance of ibrutinib resistance. <b>Methods:</b> We examined 28 patients' peripheral blood (PB) samples (treatment naïve, ibrutinib sensitive, clinically ibrutinib resistant). The surface markers' expression (CD27, CD69, CD86, CD184, CD185) were measured by flow cytometry. Furthermore, the BTK^C481S resistance mutation was assessed by digital droplet PCR. Moreover, the CLL cells' phenotype of a patient with acquired ibrutinib resistance was observed during the ibrutinib treatment. <b>Results:</b> The expression of CD27 (<i>p</i> = 0.030) and CD86 (<i>p</i> = 0.031) became higher in the clinically resistant cohort than in the ibrutinib sensitive cohort. Besides, we found that high CD86 and CD27 expressions were accompanied by BTK^C481S mutation. Our prospective study showed that the increase of the expression of CD27, CD69 and CD86 was noticed ahead of the clinical resistance with 3 months. <b>Conclusion:</b> Our study suggests that the changes of the expression of these markers could indicate ibrutinib resistance and the examination of these phenotypic changes may become a part of the patients' follow-up in the future.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610659"},"PeriodicalIF":2.8,"publicationDate":"2022-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33496007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Diagnostic Exosomal LncRNA-miRNA-mRNA Biomarkers in Colorectal Cancer Based on the ceRNA Network.","authors":"Yajing Zhao,&nbsp;Xingguo Song,&nbsp;Xianrang Song,&nbsp;Li Xie","doi":"10.3389/pore.2022.1610493","DOIUrl":"https://doi.org/10.3389/pore.2022.1610493","url":null,"abstract":"<p><p><b>Background:</b> Colorectal cancer (CRC) is currently the fourth most common cancer worldwide. The roles of exosomal competing endogenous RNAs (ceRNAs) in CRC remain unclear. In this study, we constructed an exosomal ceRNA network to identify the core ceRNAs and investigate the diagnostic biomarkers in CRC. <b>Methods and Patients:</b> Serum exosomes were isolated from four CRC patients and two healthy donors by ultracentrifugation, and then subjected to RNA isolation, sequencing and microarray. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were performed to identify functional enrichment implications of differentially expressed exosomal mRNAs. TargetScan and miRanda were used for identifying the miRNA-mRNA and miRNA-LncRNA interactions. The predicted lncRNAs and mRNAs were intersected with the differentially expressed genes, for which the screening criterion was fold change >1.5 in the microarray. Differentially expressed exosomal miRNAs were identified in the GSE71008 dataset, and differentially expressed mRNAs (DEmRNAs) were further summarized from The Cancer Genome Atlas (TCGA) database. <b>Results:</b> A total of 1186 exosomal DEmRNAs, 2088 exosomal DElncRNAs and 29 exosomal miRNAs were detected in CRC patients compared to the healthy donors. Functional enrichment analysis suggested that exosomal DEmRNAs might participate in pathways related to carcinogenesis and development of cancer. An exosomal ceRNA regulatory network of CRC was constructed based on 40 lncRNAs, two miRNAs, and five mRNAs. Exosomal miR-150-5p and miR-10b-5p expression levels were increased in healthy donors compared with CRC patients in the GSE71008 dataset, and five DEmRNAs (<i>TOMM70A</i>, <i>RBM48</i>, <i>BEND3</i>, <i>RHOBTB1</i>, and <i>ADAMTS2</i>) were significantly upregulated in TCGA database. Two potential exosomal regulatory axes of lncRNA G016261-miR-150-5p-<i>RBM48</i> and lncRNA XLOC_011677-miR-10b-5p-<i>BEND3</i> were identified from the network. <b>Conclusion:</b> The current study revealed potential molecular biological regulation pathways and diagnostic biomarkers through the exosomal ceRNA regulatory network.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610493"},"PeriodicalIF":2.8,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40388836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a Novel Prognostic Prediction Model for Gastric Cancer Based on Necroptosis-Related Genes.","authors":"Zhong-Zhong Zhu,&nbsp;Guanglin Zhang,&nbsp;Jianping Liu","doi":"10.3389/pore.2022.1610641","DOIUrl":"https://doi.org/10.3389/pore.2022.1610641","url":null,"abstract":"<p><p><b>Background:</b> Necroptosis plays a crucial role in the progression of multiple types of cancer. However, the role of necroptosis in gastric cancer (GC) remains unclear. The aim of this study is to establish a necroptosis-related prediction model, which could provide information for treatment monitoring. <b>Methods:</b> The TCGA-STAD cohort was employed to establish a prognostic prediction signature and the GEO dataset was employed for external validation. The correlation between the risk score and the immune landscape, tumor mutational burden (TMB), microsatellite instability (MSI), as well as therapeutic responses of different therapies were analyzed. <b>Results:</b> We constructed a prognostic model based on necroptosis-associated genes (NAGs), and its favorable predictive ability was confirmed in an external cohort. The risk score was confirmed as an independent determinant, and a nomogram was further established for prognosis. A high score implies higher tumor immune microenvironment (TIME) scores and more significant TIME cell infiltration. High-risk patients presented with lower TMB, and low-TMB patients had worse overall survival (OS). Meanwhile, Low-risk scores are characterized by MSI-high (MSI-H), lower Tumor Immune Dysfunction and Exclusion (TIDE) score, and higher immunogenicity in immunophenoscore (IPS) analysis. <b>Conclusion:</b> The developed NAG score provides a novel and effective method for predicting the outcome of GC as well as potential targets for further research.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610641"},"PeriodicalIF":2.8,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40390270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic <i>NUP214</i>::<i>ABL1</i> Gene Fusion.","authors":"Egle Stukaite-Ruibiene,&nbsp;Rimvydas Norvilas,&nbsp;Vaidas Dirse,&nbsp;Sigita Stankeviciene,&nbsp;Goda Elizabeta Vaitkeviciene","doi":"10.3389/pore.2022.1610570","DOIUrl":"https://doi.org/10.3389/pore.2022.1610570","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) with recurrent genetic lesions, affecting a series of kinase genes, is associated with unfavorable prognosis, however, it could benefit from treatment with tyrosine kinase inhibitors (TKI). <i>NUP214</i>::<i>ABL1</i> fusion is detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL), and is very rare in B-ALL. We present a case of adolescent with B-ALL and a cryptic <i>NUP214</i>::<i>ABL1</i> fusion which was initially missed during diagnostic screening and was detected by additional RNA sequencing. Treatment with specific ABL-inhibitor Imatinib was added later in therapy with a good effect. Initial treatment according to conventional chemotherapy was complicated by severe side effects. At the end of Consolidation, the patient was stratified to a high risk group with allogeneic hematopoietic stem cell transplantation because of insufficient response to therapy. At that time, targeted RNA sequencing detected <i>NUP214</i>::<i>ABL1</i> gene fusion which was previously missed due to a small microduplication in the 9q34 chromosome region. Gene variant analysis revealed no TKI-resistant <i>ABL1</i> mutations; therefore, treatment with Imatinib was added to target the <i>NUP214::ABL1</i> fusion protein. A negative minimal residual disease was achieved, and treatment was downgraded to intermediate risk protocol. Combining routine genetic assays with next-generation sequencing methods could prevent from missing atypical gene alterations. Identification of rare targetable genetic subtypes is of importance in order to introduce targeted therapy as early as possible that may improve survival and reduce toxicity. Treatment with ABL1 inhibitor imatinib mesylate revealed as a highly effective targeted therapy against the leukemia driving protein kinase.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610570"},"PeriodicalIF":2.8,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40381544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: The Role of Time as a Prognostic Factor in Pediatric Brain Tumors: a Multivariate Survival Analysis.","authors":"Pathology And Oncology Research Production Office","doi":"10.3389/pore.2022.1610756","DOIUrl":"https://doi.org/10.3389/pore.2022.1610756","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1007/s12253-020-00875-3.].</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610756"},"PeriodicalIF":2.8,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33481988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pathologic Complete Response Ratio of Liver Metastases Represents a Valuable Prognostic Indicator.","authors":"Yanbo Xu,&nbsp;Jiarui He,&nbsp;Weihao Li,&nbsp;Weili Zhang,&nbsp;Songran Liu,&nbsp;Jiahua He,&nbsp;Zhizhong Pan,&nbsp;Zhenhai Lu,&nbsp;Jianhong Peng,&nbsp;Junzhong Lin","doi":"10.3389/pore.2022.1610663","DOIUrl":"https://doi.org/10.3389/pore.2022.1610663","url":null,"abstract":"<p><p><b>Background and Objectives:</b> The aim of this study was to evaluate the role of the pathologic complete response ratio of liver metastases (PCRRLM) in predicting the prognosis and recurrence of colorectal cancer liver metastases (CRLM). <b>Methods:</b> A total of 305 CRLM patients who underwent preoperative chemotherapy followed by hepatectomy were included. PCRRLM was defined as the number of liver metastases exhibiting pathologic complete response (PCR) divided by the number of total resected liver metastases. The Kaplan-Meier method was used to calculate survival, and differences were examined by the log-rank test. Univariate and multivariate analyses were performed to identify the predictors of PCRRLM, recurrence-free survival (RFS) and overall survival (OS). <b>Results:</b> Among the 305 included patients, 44 (14.4%) achieved a PCRRLM ≥0.50 (including PCRRLM = 1), and 261 (85.6%) achieved a PCRRLM <0.50 (including PCRRLM = 0). Patients of an older age (≥55 years old) and those with higher carcinoembryonic antigen (CEA) levels (≥5 ng/ml) were less likely to achieve a PCRRLM ≥0.50. In the multivariate analysis, PCRRLM≥ 0.50 (vs. < 0.50, HR [95% CI]: 0.67 [0.46-0.99], <i>p</i> = 0.043) was associated with better RFS. Positive lymph node status (vs. negative, HR [95% CI]: 1.46 [1.04-2.05], <i>p</i> = 0.028) and TBS ≥5 (vs. < 5, HR [95% CI]: 1.44 [1.02-2.04], <i>p</i> = 0.038) were associated with worse RFS. <b>Conclusion:</b> PCRRLM was significantly associated with long-term RFS after preoperative chemotherapy and CRLM resection. Thus, it may be a valuable indicator of recurrence in CRLM patients.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610663"},"PeriodicalIF":2.8,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33478367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Natural Killer Cell-Mediated Cancer Immunotherapy by the Biological Macromolecule <i>Nocardia rubra</i> Cell-Wall Skeleton.","authors":"Jie Wu,&nbsp;Baojun He,&nbsp;Miao Miao,&nbsp;Xibin Han,&nbsp;Hongyan Dai,&nbsp;Heng Dou,&nbsp;Yanqiu Li,&nbsp;Xiaoqing Zhang,&nbsp;Guangchuan Wang","doi":"10.3389/pore.2022.1610555","DOIUrl":"https://doi.org/10.3389/pore.2022.1610555","url":null,"abstract":"<p><p>The biological macromolecule <i>Nocardia rubra</i> cell-wall skeleton (Nr-CWS) has well-established immune-stimulating and anti-tumor activities. However, the role of Nr-CWS on natural killer (NK) cells remains unclear. Here, we explore the function and related mechanisms of Nr-CWS on NK cells. Using a tumor-bearing model, we show that Nr-CWS has slightly effect on solid tumor. In addition, using a tumor metastasis model, we show that Nr-CWS suppresses the lung metastasis induced by B16F10 melanoma cells in mice, which indicates that Nr-CWS may up-regulate the function of NK cells. Further investigation demonstrated that Nr-CWS can increase the expression of TRAIL and FasL on spleen NK cells from Nr-CWS treated B16F10 tumor metastasis mice. The spleen index and serum levels of TNF-α, IFN-γ, and IL-2 in B16F10 tumor metastasis mice treated with Nr-CWS were significantly increased. <i>In vitro</i>, the studies using purified or sorted NK cells revealed that Nr-CWS increases the expression of CD69, TRAIL, and FasL, decreases the expression of CD27, and enhances NK cell cytotoxicity. The intracellular expression of IFN-γ, TNF-α, perforin (prf), granzyme-B (GrzB), and secreted TNF-α, IFN-γ, IL-6 of the cultured NK cells were significantly increased after treatment with Nr-CWS. Overall, the findings indicate that Nr-CWS could suppress the lung metastasis induced by B16F10 melanoma cells, which may be exerted through its effect on NK cells by promoting NK cell terminal differentiation (CD27^lowCD11b^high), and up-regulating the production of cytokines and cytotoxic molecules.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610555"},"PeriodicalIF":2.8,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40360616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}