Cellular Oncology最新文献

{"title":"ITGB2-ICAM1 axis promotes liver metastasis in BAP1-mutated uveal melanoma with retained hypoxia and ECM signatures.","authors":"Jiaoduan Li, Dongyan Cao, Lixin Jiang, Yiwen Zheng, Siyuan Shao, Ai Zhuang, Dongxi Xiang","doi":"10.1007/s13402-023-00908-4","DOIUrl":"10.1007/s13402-023-00908-4","url":null,"abstract":"<p><strong>Purpose: </strong>Uveal melanoma (UM) with BAP1 inactivating mutations has a high risk of metastasis, but the mechanism behind BAP1 deficiency driving UM metastasis is unknown.</p><p><strong>Methods: </strong>We analyzed the single-cell RNA sequencing (scRNA-Seq) data comprised primary and metastatic UM with or without BAP1 mutations (MUTs) to reveal inter- and intra-tumor heterogeneity among different groups. Then, an immune-competent mouse liver metastatic model was used to explore the role of ITGB2-ICAM1 in BAP1-associated UM metastasis.</p><p><strong>Results: </strong>Cluster 1 tumor cells expressed high levels of genes linked to tumor metastasis, such as GDF15, ATF3, and CDKN1A, all of which are associated with poor prognosis. The strength of communication between terminally exhausted CD8⁺ T cells and GDF15^hiATF3^hiCDKN1A^hi tumor cells was enhanced in BAP1-mutated UM, with CellChat analysis predicting strong ITGB2-ICAM1 signaling between them. High expression of either ITGB2 or ICAM1 was a worse prognostic indicator. Using an immune-competent mouse liver metastatic model, we indicated that inhibiting either ICAM1 or ITGB2 prevented liver metastasis in the BAP1-mutated group in vivo. The inhibitors primarily inhibited hypoxia- and ECM-related pathways indicated by changes in the expression of genes such as ADAM8, CAV2, ENO1, PGK1, LOXL2, ITGA5, and VCAN. etc. CONCLUSION: This study suggested that the ITGB2-ICAM1 axis may play a crucial role for BAP1-associated UM metastasis by preserving hypoxia- and ECM- related signatures, which provide a potential strategy for preventing UM metastasis in patients with BAP1 mutation.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"951-965"},"PeriodicalIF":4.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OTUB1 accelerates hepatocellular carcinoma by stabilizing RACK1 via its non-canonical ubiquitination.","authors":"Liqun Peng, Tiangen Wu, Yingyi Liu, Dongli Zhao, Wenzhi He, Yufeng Yuan","doi":"10.1007/s13402-023-00913-7","DOIUrl":"10.1007/s13402-023-00913-7","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated ubiquitination modification occupies a pivotal role in hepatocellular carcinoma (HCC) tumorigenesis and progression. The ubiquitin aldehyde binding 1 (OTUB1) was aberrantly upregulated and exhibited the pro-tumorigenic function in HCC. However, the underlying mechanisms and responsible targets of OTUB1 remain unclear.</p><p><strong>Methods: </strong>First, bioinformatics analysis, western blot and immunohistochemistry staining were applied to analyze OTUB1 expression in HCC specimens. Then, immunoprecipitation assay-tandem mass spectrometry (MS) combined with the gene set enrichment analysis (GSEA) was used to explore the downstream target of OTUB1. Co-immunoprecipitation and ubiquitination assays were used to identify the mechanisms involved. Finally, we explored the regulatory effect of MAZ on OTUB1 through ChIP-qPCR and dual-luciferase reporter assay.</p><p><strong>Results: </strong>OTUB1 was broadly elevated in HCC tissues and promoted the proliferation and metastasis of HCC in vitro and in vivo. The receptor for activated C kinase 1 (RACK1) performed as a functional partner of OTUB1 and its hyperactivation was associated with aggressive development and other malignant features in HCC by activating oncogenes transcription. Mechanistically, OTUB1 directly bound to RACK1 at its C-terminal domain and decreased the K48-linked ubiquitination of RACK1 through its non-canonical suppression of ubiquitination activity, which stabilized RACK1 protein levels in HCC cells. Therefore, OTUB1 significantly increased multiple oncogenes expression and activated PI3K/AKT and FAK/ERK signaling in a RACK1-dependent manner in HCC. Moreover, the transcription factor MAZ upregulated OTUB1 expression through identifying a putative response element of OTUB1 promoter area.</p><p><strong>Conclusions: </strong>Our findings might provide a new therapeutic strategy for HCC by modifying the MAZ-OTUB1-RACK1 axis.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"987-1004"},"PeriodicalIF":4.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stiffened tumor microenvironment enhances perineural invasion in breast cancer via integrin signaling.","authors":"Bing Han, Xin Guan, Mingyue Ma, Baoling Liang, Linglie Ren, Yutong Liu, Ye Du, Shu-Heng Jiang, Dong Song","doi":"10.1007/s13402-023-00901-x","DOIUrl":"10.1007/s13402-023-00901-x","url":null,"abstract":"<p><strong>Background: </strong>Accumulating studies have shown that tumors are regulated by nerves, and there is abundant nerve infiltration in the tumor microenvironment. Many solid tumors including breast cancer (BRCA) have different degrees of perineural invasion (PNI), which is closely related to the tumor occurrence and progression. However, the regulatory mechanism of PNI in BRCA remains largely unexplored.</p><p><strong>Methods: </strong>PNI-related molecular events are analyzed by the RNAseq data of BRCA samples deposited in The Cancer Genome Atlas (TCGA) database. Extracellular matrix (ECM) components within the tumor microenvironment are analyzed by immunohistochemical staining of α-SMA, Sirius red staining, and Masson trichrome staining. Soft and stiff matrix gels, living cell imaging, and dorsal root ganglion (DRG) coculture assay are used to monitor cancer cell invasiveness towards nerves. Western blotting, qRT-PCR, enzyme-linked immunosorbent assay combined with neutralizing antibody and small molecular inhibitors are employed to decode molecular mechanisms.</p><p><strong>Results: </strong>Comparative analysis that the ECM was significantly associated with PNI status in the TCGA cohort. BRCA samples with higher α-SMA activity, fibrillar collagen, and collagen content had higher frequency of PNI. Compared with soft matrix, BRCA cells cultured in stiff matrix not only displayed higher cell invasiveness to DRG neurons but also had significant neurotrophic effects. Mechanistically, integrin β1 was identified as a functional receptor to the influence of stiff matrix on BRCA cells. Moreover, stiffened matrix-induced activation of integrin β1 transduces FAK-YAP signal cascade, which enhances cancer invasiveness and the neurotrophic effects. In clinical setting, PNI-positive BRCA samples had higher expression of ITGB1, phosphorylated FAK, YAP, and NGF compared with PNI-negative BRCA samples.</p><p><strong>Conclusions: </strong>Our findings suggest that stiff matrix induces expression of pro-metastatic and neurotrophic genes through integrin β1-FAK-YAP signals, which finally facilitates PNI in BRCA. Thus, our study provides a new mechanism for PNI in BRCA and highlights nerve-based tumor treatment strategies.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"867-882"},"PeriodicalIF":4.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138446721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting MEK/COX-2 axis improve immunotherapy efficacy in dMMR colorectal cancer with PIK3CA overexpression.","authors":"Kunwei Peng, Yongxiang Liu, Shousheng Liu, Zining Wang, Huanling Zhang, Wenzhuo He, Yanan Jin, Lei Wang, Xiaojun Xia, Liangping Xia","doi":"10.1007/s13402-024-00916-y","DOIUrl":"10.1007/s13402-024-00916-y","url":null,"abstract":"<p><strong>Purpose: </strong>PIK3CA mutation or overexpression is associated with immunotherapy resistance in multiple cancer types, but is also paradoxically associated with benefit of COX-2 inhibition on patient survival of colorectal cancer (CRC) with mismatch repair deficiency (dMMR). This study examined whether and how PIK3CA status affected COX-2-mediated tumor inflammation and immunotherapy response of dMMR CRC.</p><p><strong>Methods: </strong>Murine colon cancer cells MC38, CT26, and CT26-Mlh1-KO were used to construct PIK3CA knockdown and overexpression models to mimic dMMR CRC with PIK3CA dysregulation, and xenograft models were used to evaluate how PIK3CA regulate COX-2 expression, CD8⁺ T cells infiltration, tumor growth, and therapy response to anti-PD-L1 treatment using immunocompetent mice. Western blot was carried out to delineate the signaling pathways in human and mouse cancer cells, and immunohistochemical analysis together with bioinformatics analysis using human patient samples.</p><p><strong>Results: </strong>PIK3CA upregulates COX-2 expression through MEK/ERK signaling pathway independent of AKT signaling to promote tumor inflammation and immunosuppression. PIK3CA knockdown profoundly reduced CT26 tumor growth in a CD8⁺ T cell-dependent manner, while PIK3CA overexpression significantly inhibited CD8⁺ T cells infiltration and promoted tumor growth. Furthermore, MEK or COX-2 inhibition augmented the anti-tumor activity of anti-PD-L1 immunotherapy on dMMR CRC mouse models, accompanied with increased CD8⁺ T cells infiltration and activated tumor microenvironment.</p><p><strong>Conclusion: </strong>Our results identified that the PIK3CA hyperactivation in dMMR CRC upregulated COX-2 through MEK signaling, which inhibited CD8⁺ T cells infiltration and promoted tumor growth, together led to immunotherapy resistance. COX-2 or MEK inhibition may relieve therapy resistance and promote therapy efficacy of anti-PD-1/PD-L1 immunotherapy for treating dMMR CRC with PIK3CA overexpression or activating mutation.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1043-1058"},"PeriodicalIF":4.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NK cells as powerful therapeutic tool in cancer immunotherapy.","authors":"Mao Huang, Yixuan Liu, Qijia Yan, Miao Peng, Junshang Ge, Yongzhen Mo, Yumin Wang, Fuyan Wang, Zhaoyang Zeng, Yong Li, Chunmei Fan, Wei Xiong","doi":"10.1007/s13402-023-00909-3","DOIUrl":"10.1007/s13402-023-00909-3","url":null,"abstract":"<p><strong>Background: </strong>Natural killer (NK) cells have gained considerable attention and hold great potential for their application in tumor immunotherapy. This is mainly due to their MHC-unrestricted and pan-specific recognition capabilities, as well as their ability to rapidly respond to and eliminate target cells. To artificially generate therapeutic NK cells, various materials can be utilized, such as peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK cell lines. Exploiting the therapeutic potential of NK cells to treat tumors through in vivo and in vitro therapeutic modalities has yielded positive therapeutic results.</p><p><strong>Conclusion: </strong>This review provides a comprehensive description of NK cell therapeutic approaches for tumors and discusses the current problems associated with these therapeutic approaches and the prospects of NK cell therapy for tumors.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"733-757"},"PeriodicalIF":4.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-GlcNAcylation of TRIM29 and OGT translation forms a feedback loop to promote adaptive response of PDAC cells to glucose deficiency.","authors":"Fu-Ying Zhao, Xue Chen, Jia-Mei Wang, Ye Yuan, Chao Li, Jia Sun, Hua-Qin Wang","doi":"10.1007/s13402-023-00915-5","DOIUrl":"10.1007/s13402-023-00915-5","url":null,"abstract":"<p><strong>Purpose: </strong>Glucose not only provides energy for tumor cells, but also provides various biomolecules that are essential for their survival, proliferation and invasion. Therefore, it is of great clinical significance to understand the mechanism of how tumor cells adapt to metabolic stress and maintain their survival. The aim of this research was to study the critical role of OGT and TRIM29 O-GlcNAc modification driven adaptability of PDAC cells to low glucose stress, which might have important medical implications for PDAC therapy.</p><p><strong>Methods: </strong>Western blotting, mass spectrometry and WGA-immunoprecipitation were used to examined the levels of OGT and O-GlcNAc glycosylated proteins in BxPC3 and SW1990 cells in normal culture and under glucose deprivation conditions. Crystal violet assay, flow cytometry, RIP, RT-qPCR, protein stability assay, biotin pull down were used to investigate the mechanism of OGT and TRIM29-mediated adaptive response to glucose deficiency in PDAC cells.</p><p><strong>Results: </strong>The current study found that under the condition of low glucose culture, the levels of OGT and O-GlcNAc glycosylation in PDAC cells were significantly higher than those in normal culture. Moreover, the high expression of OGT has a protective effect on PDAC cells under low glucose stress. This study confirmed that there was no significant change in mRNA level and protein degradation of OGT under low glucose stress, which was mainly reflected in the increase of protein synthesis. In addition, O-GlcNAc modification at T120 site plays a critical role in the metabolic adaptive responses mediated by TRIM29.</p><p><strong>Conclusions: </strong>Taken together, our study indicated that O-GlcNAcylation of TRIM29 at T120 site and OGT translation forms a loop feedback to facilitate survival of PDAC under glucose deficiency.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1025-1041"},"PeriodicalIF":4.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing AHNAK promotes nasopharyngeal carcinoma progression by upregulating the ANXA2 protein.","authors":"Xingxing Lu, Yan Mei, Chunmei Fan, Pan Chen, Xiayu Li, Zhaoyang Zeng, Guiyuan Li, Wei Xiong, Bo Xiang, Mei Yi","doi":"10.1007/s13402-023-00898-3","DOIUrl":"10.1007/s13402-023-00898-3","url":null,"abstract":"<p><strong>Purpose: </strong>Nasopharyngeal carcinoma (NPC) is an aggressive head and neck disease with a high incidence of distant metastases. Enlargeosomes are cytoplasmic organelles marked by, desmoyokin/AHNAK. This study aimed to evaluate the expression of AHNAK in NPC and its effect on enlargeosomes and to investigate the correlation between AHNAK expression levels and clinical NPC patient characteristics.</p><p><strong>Methods: </strong>Primary nasopharyngeal carcinoma (NPC) and NPC specimens were evaluated by analyzing public data, and immunohistochemistry. Systematic in vitro and in vivo experiments were performed using different NPC-derived cell lines and mouse models.</p><p><strong>Results: </strong>In this study, we detected AHNAK and Annexin A2(ANXA2), a protein coating the surface of enlargeosomes, in NPC samples. We found that AHNAK was down-regulated. Down-regulation of AHNAK was associated with poor overall survival in NPC patients. Moreover, transcription factor FOSL1-mediated transcriptional repression was responsible for the low expression of AHNAK by recruiting EZH2. Whereas Annexin A2 was upregulated in human NPC tissues. Upregulation of Annexin A2 was associated with lymph node metastasis and distant metastasis in NPC patients. Functional studies confirmed that silencing of AHNAK enhanced the growth, invasion, and metastatic properties of NPC cells both in vitro and in vivo. In terms of mechanism, loss of AHNAK led to an increase of annexin A2 protein level in NPC cells. Silencing ANXA2 restored NPC cells' migrative and invasive ability upon loss of AHNAK.</p><p><strong>Conclusion: </strong>Here, we report AHNAK as a tumor suppressor in NPC, which may act through annexin A2 oncogenic signaling in enlargeosome, with potential implications for novel approaches to NPC treatment.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"833-850"},"PeriodicalIF":4.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying cancer subtypes based on embryonic and hematopoietic stem cell signatures in pan-cancer.","authors":"Jiali Lei, Jiangti Luo, Qian Liu, Xiaosheng Wang","doi":"10.1007/s13402-023-00886-7","DOIUrl":"10.1007/s13402-023-00886-7","url":null,"abstract":"<p><strong>Purpose: </strong>Cancer cells with stem cell-like properties may contribute to cancer development and therapy resistance. The advancement of multi-omics technology has sparked interest in exploring cancer stemness from a multi-omics perspective. However, there is a limited number of studies that have attempted to subtype cancer by combining different types of stem cell signatures.</p><p><strong>Methods: </strong>In this study, 10,323 cancer specimens from 33 TCGA cancer types were clustered based on the enrichment scores of six stemness gene sets, representing two types of stem cell backgrounds: embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs).</p><p><strong>Results: </strong>We identified four subtypes of pan-cancer, termed StC1, StC2, StC3 and StC4, which displayed distinct molecular and clinical features, including stemness, genome integrity, intratumor heterogeneity, methylation levels, tumor microenvironment, tumor progression, responses to chemotherapy and immunotherapy, and survival prognosis. Importantly, this subtyping method for pan-cancer is reproducible at the protein level.</p><p><strong>Conclusion: </strong>Our findings indicate that the ESC signature is an adverse prognostic factor in cancer, while the HSC signature and ratio of HSC/ESC signatures are positive prognostic factors. The subtyping of cancer based on ESC and HSC signatures may provide insights into cancer biology and clinical implications of cancer.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"587-605"},"PeriodicalIF":6.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41217643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying the effectiveness of 3D culture systems to recapitulate breast tumor tissue in situ.","authors":"Katarzyna A Ludwik, Frances R Greathouse, Samuel Han, Kimberly Stauffer, David R Brenin, Thomas P Stricker, Deborah A Lannigan","doi":"10.1007/s13402-023-00877-8","DOIUrl":"10.1007/s13402-023-00877-8","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer heterogeneity contributes to chemotherapy resistance and decreased patient survival. To improve patient outcomes it is essential to develop a technology that is able to rapidly select the most efficacious therapy that targets the diverse phenotypes present within the tumor. Breast cancer organoid technologies are proposed as an attractive approach for evaluating drug responses prior to patient therapy. However, there remain challenges in evaluating the effectiveness of organoid cultures to recapitulate the heterogeneity present in the patient tumor in situ.</p><p><strong>Method: </strong>Organoids were generated from seven normal breast and nineteen breast cancer tissues diagnosed as estrogen receptor positive or triple negative. The Jensen-Shannon divergence index, a measure of the similarity between distributions, was used to compare and evaluate heterogeneity in starting tissue and their resultant organoids. Heterogeneity was analyzed using cytokeratin 8 and cytokeratin 14, which provided an easily scored readout.</p><p><strong>Results: </strong>In the in vitro culture system HER1 and FGFR were able to drive intra-tumor heterogeneity to generate divergent phenotypes that have different sensitivities to chemotherapies.</p><p><strong>Conclusion: </strong>Our methodology, which focuses on quantifiable cellular phenotypes, provides a tractable system that complements omics approaches to provide an unprecedented view of heterogeneity and will enhance the identification of novel therapies and facilitate personalized medicine.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"481-496"},"PeriodicalIF":6.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune characteristics associated with lymph node metastasis in early-stage NSCLC.","authors":"Ziyu Zhang, Li Li, Yang Gao, Xiaoxiong Xiao, Liyan Ji, Zhipeng Zhou, Juan Jiang, Shiqing Liu, Jian An, Pengbo Deng, NanNan Du, Pansong Li, Xuefeng Xia, Chengping Hu, Min Li","doi":"10.1007/s13402-023-00873-y","DOIUrl":"10.1007/s13402-023-00873-y","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor metastasis significantly impacts the prognosis of non-small cell lung cancer (NSCLC) patients, with lymph node (LN) metastasis being the most common and early form of spread. With the development of adjuvant immunotherapy, increasing attention has been paid to the tumor-draining lymph nodes（TDLN) in early-stage NSCLC, especially tumor-metastatic lymph nodes, which provides poor prognostic information but has potential benefits in adjuvant treatment.</p><p><strong>Methods: </strong>We showed the remodeled immune environment in TDLNs through using TCR-seq to analyse 24 primary lung cancer tissues and 134 LNs from 24 lung cancer patients with or without LN metastasis. Additionally, we characterized the spatial profiling of immunocytes and tumor cells in TDLNs and primary tumor sites through using multi-IHC.</p><p><strong>Results: </strong>We found the remodeled immune environment in TDLNs through analyzing primary lung cancer tissues and LNs from NSCLC patients with or without LN metastasis. Considering the intricate communication between tumor and immunocytes, we further subdivided TDLNs, revealing that metastasis-negative LNs from LN-metastatic patients (MNLN) exhibited greater immune activation, exhaustion, and memory in comparison to both metastasis-positive LNs (MPLN) and TDLNs from non-LN-metastatic patients (NMLN).</p><p><strong>Conclusions: </strong>Our data indicate that LN metastasis facilitated tumor-specific antigen presentation in TDLNs and induces T cell priming, while existing tumor cells generate an immune-suppressive environment in MPLNs through multiple mechanisms. These findings contribute to a comprehensive understanding of the immunological mechanisms through which LN metastasis influences tumor progression and plays a role in immunotherapy for NSCLC patients.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"447-461"},"PeriodicalIF":6.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}