Cancer Communications最新文献

{"title":"Nine-fold variation of risk of advanced colorectal neoplasms according to smoking and polygenic risk score: Results from a cross-sectional study in a large screening colonoscopy cohort.","authors":"Ruojin Fu, Xuechen Chen, Tobias Niedermaier, Teresa Seum, Michael Hoffmeister, Hermann Brenner","doi":"10.1002/cac2.12618","DOIUrl":"https://doi.org/10.1002/cac2.12618","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the LMP1-ALIX axis in EBV⁺ nasopharyngeal carcinoma inhibits immunosuppressive small extracellular vesicle secretion and boosts anti-tumor immunity.","authors":"Fajian He, Yan Gong, Gan Tao, Jianguo Zhang, Qiuji Wu, Yushuang Tan, Yajie Cheng, Chunsheng Wang, Jinru Yang, Linzhi Han, Zhihao Wang, Yanping Gao, Jingyi He, Rui Bai, Peikai Sun, Xiaoyan Yu, Yajuan Zhou, Conghua Xie","doi":"10.1002/cac2.12619","DOIUrl":"https://doi.org/10.1002/cac2.12619","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has revolutionized the therapeutical regimen for nasopharyngeal carcinoma (NPC), yet its response rate remains insufficient. Programmed death-ligand 1 (PD-L1) on small extracellular vesicles (sEVs) mediates local and peripheral immunosuppression in tumors, and the mechanism of PD-L1 loading into these vesicles is garnering increasing attention. Latent membrane protein 1 (LMP1), a key viral oncoprotein expressed in Epstein-Barr virus (EBV)-positive NPC, contributes to remodeling the tumor microenvironment. However, the precise mechanisms by which LMP1 modulates tumor immunity in NPC remain unclear. Here, we aimed to investigate the roles and regulatory mechanisms of LMP1 and sEV PD-L1 in NPC immune evasion.</p><p><strong>Methods: </strong>We analyzed the impact of LMP1 on tumor-infiltrating lymphocyte abundance in NPC tissues and humanized tumor-bearing mouse models using multiplex immunofluorescence (mIF) and flow cytometry, respectively. Transmission electron microscopy and nanoparticle tracking analysis were employed to characterize sEVs. Immunoprecipitation-mass spectrometry was utilized to identify proteins interacting with LMP1. The regulatory effects of sEVs on tumor microenvironment were assessed by monitoring CD8⁺ T cell proliferation and interferon-γ (IFN-γ) expression via flow cytometry. Furthermore, the expression patterns of LMP1 and downstream regulators in NPC were analyzed using mIF and survival analysis.</p><p><strong>Results: </strong>High LMP1 expression in NPC patient specimens and mouse models was associated with restricted infiltration of CD8⁺ T cells. Additionally, LMP1 promoted sEV PD-L1 secretion, leading to inhibition of CD8⁺ T cell viability and IFN-γ expression in vitro. Mechanistically, LMP1 recruited apoptosis-linked gene 2-interacting protein X (ALIX) through its intracellular domain and bound PD-L1 through its transmembrane domain, thereby facilitating the loading of PD-L1 into ALIX-dependent sEVs. Disruption of ALIX diminished LMP1-induced sEV PD-L1 secretion and enhanced the anti-tumor immunity of CD8⁺ T cells both in vitro and in vivo. Moreover, increased expression levels of LMP1 and ALIX were positively correlated with enhanced immunosuppressive features and worse prognostic outcomes in NPC patients.</p><p><strong>Conclusion: </strong>Our findings uncovered the mechanism by which LMP1 interacts with ALIX and PD-L1 to form a trimolecular complex, facilitating PD-L1 loading into ALIX-dependent sEV secretion pathway, ultimately inhibiting the anti-tumor immune response in NPC. This highlights a novel target and prognostic marker for NPC immunotherapy.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exciting progress in targeted therapy innovation for unresectable stage III EGFR-mutated NSCLC: the phase III LAURA study.","authors":"Ziyan Tong, Ning Zhu, Hong Shen, Ying Yuan","doi":"10.1002/cac2.12611","DOIUrl":"https://doi.org/10.1002/cac2.12611","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering protective genomic factors of tumor development in pediatric Down syndrome via deep learning approach to whole genome and RNA sequencing","authors":"Yichuan Liu,&nbsp;Hui-Qi Qu,&nbsp;Xiao Chang,&nbsp;Frank D Mentch,&nbsp;Haijun Qiu,&nbsp;Kenny Nguyen,&nbsp;Kayleigh Ostberg,&nbsp;Tiancheng Wang,&nbsp;Joseph Glessner,&nbsp;Hakon Hakonarson","doi":"10.1002/cac2.12612","DOIUrl":"10.1002/cac2.12612","url":null,"abstract":"&lt;p&gt;Childhood solid tumors represent a significant public health challenge worldwide, with approximately 15,000 new cases annually in the United States and an estimated 300,000 globally. Down syndrome (DS), a genetic disorder characterized by an extra full or partial copy of chromosome 21, results in distinctive developmental and physical features. Notably, individuals with DS exhibit a remarkable resilience against solid tumors compared to the general population, with an overall standardized incidence ratio (SIR) of 0.45, despite their increased susceptibility to hematologic malignancies [&lt;span&gt;1&lt;/span&gt;]. This paradoxical observation has spurred extensive research aimed at uncovering the biological underpinnings of this natural resistance to solid cancers. Current theories suggest that the overexpression of specific genes on chromosome 21 may confer protective benefits (e.g. &lt;i&gt;RCAN1&lt;/i&gt; contributes to antiangiogenic effects), and alterations in immune system function may enhance apoptosis and DNA repair pathways in individuals with trisomy 21 DS [&lt;span&gt;2&lt;/span&gt;]. The well-established epigenetic effects of trisomy 21, which influence the entire genome, are another potential contributor to the reduced risk of solid tumors [&lt;span&gt;3&lt;/span&gt;]. Nonetheless, these hypotheses face significant challenges, such as the potential oversimplification of complex genetic interactions and the lack of comprehensive genome-wide analyses. This study seeks to critically evaluate the correlations between genomic variants and cancer clinical phenotypes in patients with DS, and proposes directions for future research into the genetic and molecular mechanisms that confer cancer resistance in DS, potentially transforming our understanding and treatment of pediatric cancers.&lt;/p&gt;&lt;p&gt;We conducted an innovative unbiased data-driven analysis in 2,452 whole-genome sequencing (WGS) samples with both DS individuals (&lt;i&gt;n&lt;/i&gt; = 635) and pediatric oncology cases (&lt;i&gt;n&lt;/i&gt; = 280) within the Gabriella Miller Kids First program project (https://kidsfirstdrc.org/) housed at the Children's Hospital of Philadelphia (Supplementary Figure S1). Additionally, 284 RNA sequencing samples from human peripheral blood mononuclear cells (PBMCs), a subset of WGS samples, were also analyzed, offering unprecedented insights into the complex interplay of genetic and immunological factors influencing cancer resistance.&lt;/p&gt;&lt;p&gt;The importance of each variant was calculated using deep learning algorithms, and their corresponding weights to DS cancer were generated based on linear algebra models as described in the Supplementary Materials and Methods. There were 2,523 unique cancer protective variants identified based on deep learning algorithms combined with linear algebra models in exonic, intronic, non-coding RNA and 5’untranslated region (5’UTR) regions. The prevalence for cancer protective variants in the DS cancer group (89.2%) is significantly higher compared to non-DS cancer individuals (58.1%) (&lt;i&gt;P","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 11","pages":"1374-1378"},"PeriodicalIF":20.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic imprinting biomarkers for cervical cancer risk stratification.","authors":"Xue Xiao, Wei Wang, Peng Bai, Ying Chen, Zhengwen Qin, Tong Cheng, Xing Li, John P Pineda, Panying Shi, Xiaonan Wang, Jianhong Wang, Lian Xu, Xuemei Gao, Huixian Zheng, Lulu Yang, Wenyi Lin, Wenbin Huang, Rulong Shen, Changjun Yue, Huixiong Xu, Felipe Batalini, Yang Liu, Ning Zhou, Yaoyao Zhang, Hanmin Liu","doi":"10.1002/cac2.12617","DOIUrl":"https://doi.org/10.1002/cac2.12617","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yap methylation-induced FGL1 expression suppresses anti-tumor immunity and promotes tumor progression in KRAS-driven lung adenocarcinoma","authors":"Ji Jiang,&nbsp;Pengfei Ye,&nbsp;Ningning Sun,&nbsp;Weihua Zhu,&nbsp;Mei Yang,&nbsp;Manman Yu,&nbsp;Jingjing Yu,&nbsp;Hui Zhang,&nbsp;Zijie Gao,&nbsp;Ningjie Zhang,&nbsp;Shijie Guo,&nbsp;Yuru Ji,&nbsp;Siqi Li,&nbsp;Cuncun Zhang,&nbsp;Sainan Miao,&nbsp;Mengqi Chai,&nbsp;Wenmin Liu,&nbsp;Yue An,&nbsp;Jian Hong,&nbsp;Wei Wei,&nbsp;Shihao Zhang,&nbsp;Huan Qiu","doi":"10.1002/cac2.12609","DOIUrl":"10.1002/cac2.12609","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite significant strides in lung cancer immunotherapy, the response rates for Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>)-driven lung adenocarcinoma (LUAD) patients remain limited. Fibrinogen-like protein 1 (FGL1) is a newly identified immune checkpoint target, and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients. This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in <i>KRAS</i>-mutated cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression levels of FGL1 and SET1 histone methyltransferase (SET1A) in lung cancer were assessed using public databases and clinical samples. Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models. The effects of FGL1 and Yes-associated protein (Yap) on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry. Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A-directed transcriptional program.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Upregulation of FGL1 expression in <i>KRAS</i>-mutated cancer was inversely correlated with the infiltration of CD8⁺ T cells. Mechanistically, <i>KRAS</i> activated extracellular signal-regulated kinase 1/2 (ERK1/2), which subsequently phosphorylated SET1A and increased its stability and nuclear localization. SET1A-mediated methylation of Yap led to Yap sequestration in the nucleus, thereby promoting Yap-induced transcription of FGL1 and immune evasion in <i>KRAS</i>-driven LUAD. Notably, dual blockade of programmed cell death-1 (PD-1) and FGL1 further increased the therapeutic efficacy of anti-PD-1 immunotherapy in LUAD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>FGL1 could be used as a diagnostic biomarker of <i>KRAS</i>-mutated lung cancer, and targeting the Yap-FGL1 axis could increase the efficacy of anti-PD-1 immunotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 11","pages":"1350-1373"},"PeriodicalIF":20.1,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic atlas reveals immune and metabolism perturbation of depression in the pathogenesis of breast cancer","authors":"Lingling Wu,&nbsp;Junwei Liu,&nbsp;Yimeng Geng,&nbsp;Jianwen Fang,&nbsp;Xingle Gao,&nbsp;Jianbo Lai,&nbsp;Minya Yao,&nbsp;Shaojia Lu,&nbsp;Weiwei Yin,&nbsp;Peifen Fu,&nbsp;Wei Chen,&nbsp;Shaohua Hu","doi":"10.1002/cac2.12603","DOIUrl":"10.1002/cac2.12603","url":null,"abstract":"&lt;p&gt;Epidemiological evidence indicates that major depressive disorder (MDD) may predispose the development and prognosis of breast cancer (BC) in females [&lt;span&gt;1&lt;/span&gt;]. However, the mechanisms linking these phenotypes are not fully understood. Chronic stress, a hallmark of depression, has been underscored to affect anti-tumor immunity, tumor metabolic reprogramming, hormone synthesis in BC [&lt;span&gt;2, 3&lt;/span&gt;], and increase tumor metastasis [&lt;span&gt;4&lt;/span&gt;], but there is a lack of detailed cellular-level characterization of how MDD history affects the tumorigenesis of BC. This study explored the single-cell atlas of multiple tissues from BC patients with and without a history of MDD for characterizing the potential molecular alternations in their tumorigenesis (Figure 1A).&lt;/p&gt;&lt;p&gt;Paired primary tumor tissues (&lt;i&gt;n&lt;/i&gt; = 10), adjacent normal tissues (&lt;i&gt;n&lt;/i&gt; = 7), and peripheral blood samples (&lt;i&gt;n&lt;/i&gt; = 10) were collected from a cohort of 10 BC patients, 5 of whom had a history of MDD (Supplementary Table S1). All BC patients had estrogen receptor (ER)-positive tumors and were further predicted as Luminal A (&lt;i&gt;n&lt;/i&gt; = 9) and B subtypes (&lt;i&gt;n&lt;/i&gt; = 1) (Supplementary Table S2). Further details on patient recruitment, sample handling, and single-cell data analysis are provided in Supplementary Methods. In total, we obtained 224,557 single cells and further annotated them into major cell subsets based on lineage markers and copy number variations [&lt;span&gt;5&lt;/span&gt;] (Figure 1B, Supplementary Figure S1A-B). Aneuploid cells in primary tumor tissues were obtained (Supplementary Table S3) to characterize their phenotypic differences in BC patients with MDD history (BC-MDD) or not (BC-Ctrl). The Uniform Manifold Approximation and Projection (UMAP) of unintegrated aneuploid cells revealed intrinsic differences across individual patients (Supplementary Figure S1C). Downstream functional profiling analysis identified distinct immune response pathways in BC-MDD and BC-Ctrl groups and enrichment of the oxidative phosphorylation (OXPHOS) pathway in BC-Ctrl tumors (Supplementary Figure S1D-E). Cellular Gene Set Variation Analysis (GSVA) [&lt;span&gt;6&lt;/span&gt;] confirmed the distinct metabolic phenotypes between BC-MDD and BC-Ctrl groups (Figure 1C). Additionally, utilizing predefined gene module (GM) signatures of BC tumor cells [&lt;span&gt;7&lt;/span&gt;], we observed specific restraint of GM4 and GM6 in BC-MDD (Supplementary Figure S1F-G). GM6 encompasses various antigen presentation genes, aligning with the observed downregulation of major histocompatibility complex class I (MHC-I) class genes in BC-MDD tumor cells (Supplementary Figure S1H).&lt;/p&gt;&lt;p&gt;Upon re-clustering 12,371 normal epithelial cells within primary breast tumor and adjacent normal tissues from the 10 patients, we identified 9 cell clusters, including luminal hormone-responsive (LumHR), luminal secretory (LumSec), and myoepithelial cells [&lt;span&gt;8&lt;/span&gt;] (Supplementary Figure S2A-B). Distribution analysis suggested","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 11","pages":"1311-1315"},"PeriodicalIF":20.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local TSH/TSHR signaling promotes CD8+ T cell exhaustion and immune evasion in colorectal carcinoma","authors":"Sisi Zeng,&nbsp;Huiling Hu,&nbsp;Zhiyang Li,&nbsp;Qi Hu,&nbsp;Rong Shen,&nbsp;Mingzhou Li,&nbsp;Yunshi Liang,&nbsp;Zuokang Mao,&nbsp;Yandong Zhang,&nbsp;Wanqi Zhan,&nbsp;Qin Zhu,&nbsp;Feifei Wang,&nbsp;Jianbiao Xiao,&nbsp;Bohan Xu,&nbsp;Guanglong Liu,&nbsp;Yanan Wang,&nbsp;Bingsong Li,&nbsp;Shaowan Xu,&nbsp;Zhaowen Zhang,&nbsp;Ceng Zhang,&nbsp;Zhizhang Wang,&nbsp;Li Liang","doi":"10.1002/cac2.12605","DOIUrl":"10.1002/cac2.12605","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dysfunction of CD8⁺ T cells in the tumor microenvironment (TME) contributes to tumor immune escape and immunotherapy tolerance. The effects of hormones such as leptin, steroid hormones, and glucocorticoids on T cell function have been reported previously. However, the mechanism underlying thyroid-stimulating hormone (TSH)/thyroid-stimulating hormone receptor (TSHR) signaling in CD8⁺ T cell exhaustion and tumor immune evasion remain poorly understood. This study was aimed at investigating the effects of TSH/TSHR signaling on the function of CD8⁺ T cells and immune evasion in colorectal cancer (CRC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TSHR expression levels in CD8⁺ T cells were assessed with immunofluorescence and flow cytometry. Functional investigations involved manipulation of TSHR expression in cellular and mouse models to study its role in CD8⁺ T cells. Mechanistic insights were mainly gained through RNA-sequencing, Western blotting, chromatin immunoprecipitation and luciferase activity assay. Immunofluorescence, flow cytometry and Western blotting were used to investigate the source of TSH and TSHR in CRC tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TSHR was highly expressed in cancer cells and CD8⁺ T cells in CRC tissues. TSH/TSHR signaling was identified as the intrinsic pathway promoting CD8⁺ T cell exhaustion. Conditional deletion of TSHR in CD8⁺ tumor-infiltrating lymphocytes (TILs) improved effector differentiation and suppressed the expression of immune checkpoint receptors such as programmed cell death 1 (PD-1) and hepatitis A virus cellular receptor 2 (HAVCR2 or TIM3) through the protein kinase A (PKA)/cAMP-response element binding protein (CREB) signaling pathway. CRC cells secreted TSHR via exosomes to increase the TSHR level in CD8⁺ T cells, resulting in immunosuppression in the TME. Myeloid-derived suppressor cells (MDSCs) was the main source of TSH within the TME. Low expression of TSHR in CRC was a predictor of immunotherapy response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The present findings highlighted the role of endogenous TSH/TSHR signaling in CD8⁺ T cell exhaustion and immune evasion in CRC. TSHR may be suitable as a predictive and therapeutic biomarker in CRC immunotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 11","pages":"1287-1310"},"PeriodicalIF":20.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial","authors":"Yan Zheng,&nbsp;Guanghui Liang,&nbsp;Dongfeng Yuan,&nbsp;Xianben Liu,&nbsp;Yufeng Ba,&nbsp;Zimin Qin,&nbsp;Sining Shen,&nbsp;Zhenxuan Li,&nbsp;Haibo Sun,&nbsp;Baoxing Liu,&nbsp;Quanli Gao,&nbsp;Peng Li,&nbsp;Zongfei Wang,&nbsp;Shilei Liu,&nbsp;Jianping Zhu,&nbsp;Haoran Wang,&nbsp;Haibo Ma,&nbsp;Zhenzhen Liu,&nbsp;Fei Zhao,&nbsp;Jun Zhang,&nbsp;He Zhang,&nbsp;Daoyuan Wu,&nbsp;Jinrong Qu,&nbsp;Jie Ma,&nbsp;Peng Zhang,&nbsp;Wenjie Ma,&nbsp;Ming Yan,&nbsp;Yongkui Yu,&nbsp;Qing Li,&nbsp;Jiangong Zhang,&nbsp;Wenqun Xing","doi":"10.1002/cac2.12604","DOIUrl":"10.1002/cac2.12604","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m²) + cisplatin (75 mg/m²) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; <i>P</i> = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; <i>P =</i> 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; <i>P</i> = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (<i>P</i> = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 10","pages":"1214-1227"},"PeriodicalIF":20.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the routes to distant metastases in colorectal cancer: Tumor deposits and lymph node metastases as the gateway","authors":"Nelleke Pietronella Maria Brouwer,&nbsp;Ayse Selcen Oguz Erdogan,&nbsp;Shannon van Vliet,&nbsp;Natasja Rutgers,&nbsp;Nikki Knijn,&nbsp;Gesina van Lijnschoten,&nbsp;Jessica Juliana Tan,&nbsp;Johannes Hendrik Willem de Wilt,&nbsp;Niek Hugen,&nbsp;Gina Brown,&nbsp;Femke Simmer,&nbsp;Iris Dionne Nagtegaal","doi":"10.1002/cac2.12598","DOIUrl":"10.1002/cac2.12598","url":null,"abstract":"&lt;p&gt;Currently, lymph node metastases (LNM) are seen as the gateway to distant metastases in CRC and play a crucial role in the Tumor Node Metastasis (TNM) staging system [&lt;span&gt;1, 2&lt;/span&gt;]. Tumor deposits (TD) have been identified as another histological feature with a strong prognostic impact but are currently only deemed clinically relevant in the absence of LNM [&lt;span&gt;2, 3&lt;/span&gt;]. TD are clusters of tumor cells in the fat surrounding the bowel and are often associated with nerves, vessels and lymphatic tissue, giving the cancer cells access to multiple routes of spread [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;To study whether TD could indeed form an alternative gateway to distant metastases, we have used polyG-based phylogenetics on formalin-fixed paraffin-embedded (FFPE) tissue to investigate the role of histologically defined TD and LNM in CRC evolution and distant metastatic spread to the liver and peritoneum.&lt;/p&gt;&lt;p&gt;We collected data from patients who were diagnosed with colorectal liver or peritoneal metastases between January 2015 and January 2022 and not previously treated with chemotherapy. DNA was isolated from the TD and LNM (Figure 1A), normal tissue (which was sampled at the edge of the resection specimen) and distant metastases. Three distinct tissue parts of the primary tumor were sampled to account for intra-tumor heterogeneity (Figure 1B), yielding a total of 480 samples (Supplementary Table S1). Polymerase chain reaction (PCR) was used to genotype up to 24 polyG regions for every sample (Supplementary Table S2). Sequentially, phylogenetic trees were constructed based on the peak distribution of all PCR results from the polyG regions using an analysis pipeline previously developed by Naxerova et al. in R software (version 4.3.1) [&lt;span&gt;5&lt;/span&gt;]. Phylogenetic trees are graphical representations of the evolutionary relationship between biological entities, in this case, the different tissue samples. After quality control of PCR results (i.e., poor quality DNA), impurity (i.e., contamination of samples with non-tumorous cells, Supplementary Figure S1), and branching confidence (i.e., values &lt; 50% were deemed unreliable), 47 CRC patients with a total of 43 individual liver metastases and 30 individual peritoneal metastases were included in the final results (Supplementary Table S3-S5). The distribution of origins (TD, LNM, primary tumor or a mix of these) was compared between the group of liver and the group of peritoneal metastases using Fisher's exact test. Potential confounding clinicopathological factors were analyzed using the Kruskal-Wallis of Fisher's exact test. &lt;i&gt;P&lt;/i&gt; values &lt; 0.05 were considered significant. Full descriptions of the materials and methods are provided in the Supplementary Materials.&lt;/p&gt;&lt;p&gt;Phylogenetic analysis showed that the primary tumor, TD, and LNM could be possible origins of liver metastases. An exemplary phylogenetic tree is shown in Figure 1C, where different subclones gave rise to different LNMs, and sev","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 10","pages":"1209-1213"},"PeriodicalIF":20.1,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}