To better understand the complexity of the tumor microenvironment and to identify novel treatment strategies for uveal melanoma (UVM), we analyzed single-cell RNA sequencing (scRNA-seq) data from eight primary UVM eye tissues and three metastatic UVMs in the liver (GSE139829). We integrated this with bulk RNA-seq data from UVM patients derived from TCGA-UVM and GSE84976 cohorts. Our study focused on cytokine signaling in immune-related genes (CSIRGs), revealing distinct cellular compositions, intercellular interactions, and prognostic implications in UVM. We identified 137 cytokine signaling-related genes in UVM, with ISG20 significantly upregulated and linked to advanced stages and poor prognosis. Recognized for immune regulation, ISG20 emerged as a key survival predictor and therapeutic target from a risk model using Cox regression and LASSO, effectively categorizing patients by survival risk. Furthermore, differential drug response analysis revealed distinct sensitivities to drugs between the risk groups. Immune infiltration analysis showed a diverse immune landscape, potentially influencing response to immunotherapy. Structural prediction using AlphaFold 2 technology and molecular docking analyses revealed interactions between ISG20 and the therapeutic candidate decitabine. This study combines scRNA-seq analysis with structural biology approaches to unravel the molecular complexity of UVM, emphasizing the prognostic and therapeutic relevance of CSIRGs, particularly ISG20.
{"title":"Mapping the role of cytokine signaling at single-cell and structural resolution in uveal melanoma","authors":"Hongzhan Lin, Zixia Zhou, Hongyan Sun, Cunzi Li, Ying Lu, Zijing Wu, Lan Zhou, Yumo Wang, Zuhui Pu, Lisha Mou, Ming-ming Yang","doi":"10.1038/s41435-025-00337-3","DOIUrl":"10.1038/s41435-025-00337-3","url":null,"abstract":"To better understand the complexity of the tumor microenvironment and to identify novel treatment strategies for uveal melanoma (UVM), we analyzed single-cell RNA sequencing (scRNA-seq) data from eight primary UVM eye tissues and three metastatic UVMs in the liver (GSE139829). We integrated this with bulk RNA-seq data from UVM patients derived from TCGA-UVM and GSE84976 cohorts. Our study focused on cytokine signaling in immune-related genes (CSIRGs), revealing distinct cellular compositions, intercellular interactions, and prognostic implications in UVM. We identified 137 cytokine signaling-related genes in UVM, with ISG20 significantly upregulated and linked to advanced stages and poor prognosis. Recognized for immune regulation, ISG20 emerged as a key survival predictor and therapeutic target from a risk model using Cox regression and LASSO, effectively categorizing patients by survival risk. Furthermore, differential drug response analysis revealed distinct sensitivities to drugs between the risk groups. Immune infiltration analysis showed a diverse immune landscape, potentially influencing response to immunotherapy. Structural prediction using AlphaFold 2 technology and molecular docking analyses revealed interactions between ISG20 and the therapeutic candidate decitabine. This study combines scRNA-seq analysis with structural biology approaches to unravel the molecular complexity of UVM, emphasizing the prognostic and therapeutic relevance of CSIRGs, particularly ISG20.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 4","pages":"324-341"},"PeriodicalIF":4.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-09DOI: 10.1038/s41435-025-00339-1
Luna Hong, Yijiao Huang, Fengzhan Ye, Shan Wang, Yongqiang Wang, Jie Luo, Zongjiang Zhou, Junpu Wang, Xiaoqing Yuan, Nan Zhou
Tumor-associated macrophages (TAMs) promote the transition of breast cancer cells from an epithelioid to a mesenchymal phenotype (EMT) and facilitate breast cancer metastasis, but the role of lncRNA in this process is poorly understood. We employed bioinformatics analysis to identify TAMs-related lncRNAs involved in EMT, migration and metastasis of breast cancer cells. LncRNA RP11-627G18.1 was identified as a TAMs-induced lncRNA in breast cancer cells and was further evaluated using RT-qPCR. The roles of lncRNA RP11-627G18.1 in EMT and migration were further explored using RNA interference, western blot, immunofluorescence, wound healing, and transwell assays. We discovered that TAMs-related lncRNA RP11-627G18.1 is positively correlated with EMT, metastasis, and poor prognosis in breast cancer. In vitro studies showed that lncRNA RP11-627G18.1 was induced by TAMs in breast cancer cells, accompanied by enhanced EMT and migration. Knockdown of lncRNA RP11-627G18.1 reversed EMT and inhibited the migration of breast cancer cells. TAMs-induced lncRNA RP11-627G18.1 promoted EMT, migration of breast cancer cells, and tumor metastasis, suggesting it as a promising biomarker and therapeutic target for breast cancer.
{"title":"Tumor-associated macrophages-induced lncRNA RP11-627G18.1 promotes breast cancer metastasis","authors":"Luna Hong, Yijiao Huang, Fengzhan Ye, Shan Wang, Yongqiang Wang, Jie Luo, Zongjiang Zhou, Junpu Wang, Xiaoqing Yuan, Nan Zhou","doi":"10.1038/s41435-025-00339-1","DOIUrl":"10.1038/s41435-025-00339-1","url":null,"abstract":"Tumor-associated macrophages (TAMs) promote the transition of breast cancer cells from an epithelioid to a mesenchymal phenotype (EMT) and facilitate breast cancer metastasis, but the role of lncRNA in this process is poorly understood. We employed bioinformatics analysis to identify TAMs-related lncRNAs involved in EMT, migration and metastasis of breast cancer cells. LncRNA RP11-627G18.1 was identified as a TAMs-induced lncRNA in breast cancer cells and was further evaluated using RT-qPCR. The roles of lncRNA RP11-627G18.1 in EMT and migration were further explored using RNA interference, western blot, immunofluorescence, wound healing, and transwell assays. We discovered that TAMs-related lncRNA RP11-627G18.1 is positively correlated with EMT, metastasis, and poor prognosis in breast cancer. In vitro studies showed that lncRNA RP11-627G18.1 was induced by TAMs in breast cancer cells, accompanied by enhanced EMT and migration. Knockdown of lncRNA RP11-627G18.1 reversed EMT and inhibited the migration of breast cancer cells. TAMs-induced lncRNA RP11-627G18.1 promoted EMT, migration of breast cancer cells, and tumor metastasis, suggesting it as a promising biomarker and therapeutic target for breast cancer.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 4","pages":"352-364"},"PeriodicalIF":4.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-24DOI: 10.1038/s41435-025-00336-4
Kunpeng Wang, Fanyi Kong, Xue Han, Yunlai Zhi, Hai Wang, Chuanli Ren, Hui Wang
Clear cell renal carcinoma (ccRCC) is the most prevalent and aggressive subtype of kidney cancer. Targeting ccRCC metabolism is a promising therapeutic strategy, and some metabolic targets are currently undergoing clinical trials. Here, we collected multiple ccRCC clinical cohorts, including bulk RNA sequencing and single-cell sequencing datasets, to investigate mitochondrial metabolic genes’ prognostic and therapeutic potential. Integrating 10 machine learning algorithms, we constructed 117 predictive models, with the optimal model selected and defined as Mitoscore for patient stratification and treatment. Furthermore, NSUN2, an RNA 5-methylcytosine (m5C) methyltransferase, was identified as the most important gene in the model and selected for further gene function experiments in vitro and in vivo. NSUN2 promoted cell proliferation, migration, and invasion; reprogrammed glycolysis metabolism and histone lactylation levels via maintaining NEO1 mRNA stability. In addition, NSUN2 increased PD-L1 expression in tumor cells via the MYC/POM121/CD274 axis in a lactylation-dependent manner. Knockdown of NSUN2 enhanced CD8 T cell killing effects in vitro, along with TNF-α + T cell infiltration in vivo. These results highlight that mitochondrial genes are optional therapeutic targets and prognostic markers; NSUN2 promotes mitochondrial glycolysis and histone lactylation in an m5C-dependent manner, thereby resulting in PD-L1-mediated immune escape, which elucidates novel NSUN2-mediated crosstalk between glycolysis and immune evasion.
{"title":"Integrative multi-omics reveal NSUN2 facilitates glycolysis and histone lactylation-driven immune evasion in renal carcinoma","authors":"Kunpeng Wang, Fanyi Kong, Xue Han, Yunlai Zhi, Hai Wang, Chuanli Ren, Hui Wang","doi":"10.1038/s41435-025-00336-4","DOIUrl":"10.1038/s41435-025-00336-4","url":null,"abstract":"Clear cell renal carcinoma (ccRCC) is the most prevalent and aggressive subtype of kidney cancer. Targeting ccRCC metabolism is a promising therapeutic strategy, and some metabolic targets are currently undergoing clinical trials. Here, we collected multiple ccRCC clinical cohorts, including bulk RNA sequencing and single-cell sequencing datasets, to investigate mitochondrial metabolic genes’ prognostic and therapeutic potential. Integrating 10 machine learning algorithms, we constructed 117 predictive models, with the optimal model selected and defined as Mitoscore for patient stratification and treatment. Furthermore, NSUN2, an RNA 5-methylcytosine (m5C) methyltransferase, was identified as the most important gene in the model and selected for further gene function experiments in vitro and in vivo. NSUN2 promoted cell proliferation, migration, and invasion; reprogrammed glycolysis metabolism and histone lactylation levels via maintaining NEO1 mRNA stability. In addition, NSUN2 increased PD-L1 expression in tumor cells via the MYC/POM121/CD274 axis in a lactylation-dependent manner. Knockdown of NSUN2 enhanced CD8 T cell killing effects in vitro, along with TNF-α + T cell infiltration in vivo. These results highlight that mitochondrial genes are optional therapeutic targets and prognostic markers; NSUN2 promotes mitochondrial glycolysis and histone lactylation in an m5C-dependent manner, thereby resulting in PD-L1-mediated immune escape, which elucidates novel NSUN2-mediated crosstalk between glycolysis and immune evasion.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 4","pages":"312-323"},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leptin, an adipokine related to obesity, is mainly known for its role in regulating energy homeostasis and appetite by working via the leptin receptor. Recently, different groups have demonstrated that apart from adipocytes, specific cell types associated with cancer and tumor microenvironments express leptin and leptin receptors. This tumor microenvironment-associated leptin-leptin receptor signaling contributes to the different hallmarks of cancer, ranging from inflammatory changes to metastasis. Eventually, it has also been reported that high serum level of leptin, a characteristic of obese people, is linked to enhanced tumor growth. On the other hand, leptin can influence both innate as well as adaptive immunity related to cancer. Overall, leptin’s role in modulating cancer is controversial. So, in this review, we summarized the role of leptin in shaping different forms of cancer that are influenced by leptin-leptin receptor signaling with special emphasis on immunomodulation and inflammatory events and also discussed the possible therapeutic interventions to date. As this review work, with the collection of different updated knowledge, has summarized the role of leptin on cancer, it would be useful material to have on hand for both beginners as well as pioneers of these and related fields.
{"title":"A systematic review on leptin’s role in defining cancer: special emphasis on immunomodulation, inflammation, and therapeutic interventions","authors":"Snehashish Modak, Tamanna Aktar, Debabrata Majumder, Ashish Kr. Singha, Debasish Maiti","doi":"10.1038/s41435-025-00333-7","DOIUrl":"10.1038/s41435-025-00333-7","url":null,"abstract":"Leptin, an adipokine related to obesity, is mainly known for its role in regulating energy homeostasis and appetite by working via the leptin receptor. Recently, different groups have demonstrated that apart from adipocytes, specific cell types associated with cancer and tumor microenvironments express leptin and leptin receptors. This tumor microenvironment-associated leptin-leptin receptor signaling contributes to the different hallmarks of cancer, ranging from inflammatory changes to metastasis. Eventually, it has also been reported that high serum level of leptin, a characteristic of obese people, is linked to enhanced tumor growth. On the other hand, leptin can influence both innate as well as adaptive immunity related to cancer. Overall, leptin’s role in modulating cancer is controversial. So, in this review, we summarized the role of leptin in shaping different forms of cancer that are influenced by leptin-leptin receptor signaling with special emphasis on immunomodulation and inflammatory events and also discussed the possible therapeutic interventions to date. As this review work, with the collection of different updated knowledge, has summarized the role of leptin on cancer, it would be useful material to have on hand for both beginners as well as pioneers of these and related fields.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 3","pages":"266-286"},"PeriodicalIF":4.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-15DOI: 10.1038/s41435-025-00334-6
Qianwen Zheng, Shizhou Deng, Xiyu Chen, Yayun Wang, Yanling Yang
The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide, and effective treatment is urgently needed. To understand the molecular mechanisms behind the effectiveness of bariatric surgery in treating NASH, we integrated single-cell and bulk RNA sequencing data to identify the role of liver macrophage polarization in alleviating NASH and screen possible drugs for treatment. Analysis revealed that bariatric surgery alleviates NASH by inhibiting liver M1 macrophage polarization with 12 differentially expressed M1 macrophage-related genes. Additionally, 56 potentially effective drugs were predicted for NASH treatment. These findings shed light on the effectiveness of bariatric surgery in treating NASH and offer potential drug candidates for further exploration.
{"title":"Macrophage inhibition in the alleviation of nonalcoholic steatohepatitis caused by bariatric surgery","authors":"Qianwen Zheng, Shizhou Deng, Xiyu Chen, Yayun Wang, Yanling Yang","doi":"10.1038/s41435-025-00334-6","DOIUrl":"10.1038/s41435-025-00334-6","url":null,"abstract":"The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide, and effective treatment is urgently needed. To understand the molecular mechanisms behind the effectiveness of bariatric surgery in treating NASH, we integrated single-cell and bulk RNA sequencing data to identify the role of liver macrophage polarization in alleviating NASH and screen possible drugs for treatment. Analysis revealed that bariatric surgery alleviates NASH by inhibiting liver M1 macrophage polarization with 12 differentially expressed M1 macrophage-related genes. Additionally, 56 potentially effective drugs were predicted for NASH treatment. These findings shed light on the effectiveness of bariatric surgery in treating NASH and offer potential drug candidates for further exploration.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 4","pages":"297-311"},"PeriodicalIF":4.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-13DOI: 10.1038/s41435-025-00331-9
Long Shu, Tania Tao, Desheng Xiao, Shuang Liu, Yongguang Tao
Lung cancer is the deadliest cancer globally. Non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, constitutes a significant portion of cases. Adenocarcinoma, the most prevalent type, has seen a rising incidence. Immune checkpoint inhibitors (ICIs) have improved outcomes in lung adenocarcinoma (LUAD), yet response rates remain unsatisfactory. PD-1/PD-L1 inhibitors are primary ICIs for LUAD, targeting the PD-1/PD-L1 pathway between CD8+ T cells and tumor cells. However, LUAD presents a “cold tumor” phenotype with fewer CD8+ T cells and lower PD-1 expression, leading to resistance to ICIs. Thus, understanding the function of other immune cell in tumor microenvironment is crucial for developing novel immunotherapies for LUAD. B cells, which is part of the adaptive immune system, have gained attention for its role in cancer immunology. While research on B cells lags behind T cells, recent studies reveal their close correlation with prognosis and immunotherapy effectiveness in various solid tumors, including lung cancer. B cells show higher abundance, activity, and prognostic significance in LUAD than that in LUSC. This review summarizes the difference of B cell immunity between LUAD and other lung cancers, outlines the role of B cell immunity in LUAD.
{"title":"The role of B cell immunity in lung adenocarcinoma","authors":"Long Shu, Tania Tao, Desheng Xiao, Shuang Liu, Yongguang Tao","doi":"10.1038/s41435-025-00331-9","DOIUrl":"10.1038/s41435-025-00331-9","url":null,"abstract":"Lung cancer is the deadliest cancer globally. Non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, constitutes a significant portion of cases. Adenocarcinoma, the most prevalent type, has seen a rising incidence. Immune checkpoint inhibitors (ICIs) have improved outcomes in lung adenocarcinoma (LUAD), yet response rates remain unsatisfactory. PD-1/PD-L1 inhibitors are primary ICIs for LUAD, targeting the PD-1/PD-L1 pathway between CD8+ T cells and tumor cells. However, LUAD presents a “cold tumor” phenotype with fewer CD8+ T cells and lower PD-1 expression, leading to resistance to ICIs. Thus, understanding the function of other immune cell in tumor microenvironment is crucial for developing novel immunotherapies for LUAD. B cells, which is part of the adaptive immune system, have gained attention for its role in cancer immunology. While research on B cells lags behind T cells, recent studies reveal their close correlation with prognosis and immunotherapy effectiveness in various solid tumors, including lung cancer. B cells show higher abundance, activity, and prognostic significance in LUAD than that in LUSC. This review summarizes the difference of B cell immunity between LUAD and other lung cancers, outlines the role of B cell immunity in LUAD.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 3","pages":"253-265"},"PeriodicalIF":4.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, numerous studies have provided evidence of the involvement of the Golgi apparatus (GA) in various stages of cancer development. Nonetheless, the specific impact of GA-related characteristics on gastric cancer (GC) progression remains ambiguous. We utilized LASSO and multivariate COX regression methods to develop a GA-associated risk score (GARS). The GARS is constructed from seven signature genes, which are highly expressed in tumors. In our research, we have found that GARS is an effective indicator for predicting the prognosis of GC, chemotherapy sensitivity, and immune therapy response. Patients in the low GARS group exhibit characteristics such as a good prognosis, increased sensitivity to immune therapy, 5-fluorouracil, and paclitaxel. Finally, our experimental results confirm that knocking down F2R significantly reduces the proliferation and migration abilities of GC cells. This study highlights the importance of GA characteristics in predicting the prognosis of GC and in developing personalized treatment strategies. The experimental findings on F2R offer valuable theoretical insights for the diagnosis and management of GC.
{"title":"A Golgi apparatus-related signature predicts the immune microenvironment and prognosis of gastric cancer","authors":"Changlei Wu, Liang Sun, Wenjie Zhu, Chao Huang, Zhengming Zhu, Zitao Liu","doi":"10.1038/s41435-025-00332-8","DOIUrl":"10.1038/s41435-025-00332-8","url":null,"abstract":"In recent years, numerous studies have provided evidence of the involvement of the Golgi apparatus (GA) in various stages of cancer development. Nonetheless, the specific impact of GA-related characteristics on gastric cancer (GC) progression remains ambiguous. We utilized LASSO and multivariate COX regression methods to develop a GA-associated risk score (GARS). The GARS is constructed from seven signature genes, which are highly expressed in tumors. In our research, we have found that GARS is an effective indicator for predicting the prognosis of GC, chemotherapy sensitivity, and immune therapy response. Patients in the low GARS group exhibit characteristics such as a good prognosis, increased sensitivity to immune therapy, 5-fluorouracil, and paclitaxel. Finally, our experimental results confirm that knocking down F2R significantly reduces the proliferation and migration abilities of GC cells. This study highlights the importance of GA characteristics in predicting the prognosis of GC and in developing personalized treatment strategies. The experimental findings on F2R offer valuable theoretical insights for the diagnosis and management of GC.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 3","pages":"242-252"},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-06DOI: 10.1038/s41435-025-00329-3
Xin-tao Yu, Jian Cui, Xing-guo Yang, Xiang Gao, Lei Yu
Due to the covert onset of thymoma, nearly 30% of patients are diagnosed at stage III or IV, losing the opportunity for surgical treatment. We have initiated the application of prednisone in treating refractory thymoma and explored biomarkers to identify potential cases that might benefit from prednisone treatment. In a study involving 96 patients with thymoma, we confirmed a significant tumor shrinkage with prednisone acetate treatment. A reduced diameter ratio indicated that type B1 and B2 thymomas exhibited the most obvious response to prednisone acetate, especially type B2 thymoma. However, the reduced diameter ratio was < 30% in type A, AB, and B3 thymomas. Immunofluorescence and flow cytometry of tumor tissues indicated that TEMRA (T Effector Memory-Expressing CD45RA) cells primarily exist in type B thymoma. However, the percentage of interleukin-8 + TEMRA cells decreased only in B1 and B2 thymoma tissues after prednisone acetate treatment. These findings are particularly significant for patients with type B thymoma with stage III or IV.
{"title":"Novel modulation of T effector memory cells-expressing CD45RA by prednisone in inoperable advanced type B thymoma patients","authors":"Xin-tao Yu, Jian Cui, Xing-guo Yang, Xiang Gao, Lei Yu","doi":"10.1038/s41435-025-00329-3","DOIUrl":"10.1038/s41435-025-00329-3","url":null,"abstract":"Due to the covert onset of thymoma, nearly 30% of patients are diagnosed at stage III or IV, losing the opportunity for surgical treatment. We have initiated the application of prednisone in treating refractory thymoma and explored biomarkers to identify potential cases that might benefit from prednisone treatment. In a study involving 96 patients with thymoma, we confirmed a significant tumor shrinkage with prednisone acetate treatment. A reduced diameter ratio indicated that type B1 and B2 thymomas exhibited the most obvious response to prednisone acetate, especially type B2 thymoma. However, the reduced diameter ratio was < 30% in type A, AB, and B3 thymomas. Immunofluorescence and flow cytometry of tumor tissues indicated that TEMRA (T Effector Memory-Expressing CD45RA) cells primarily exist in type B thymoma. However, the percentage of interleukin-8 + TEMRA cells decreased only in B1 and B2 thymoma tissues after prednisone acetate treatment. These findings are particularly significant for patients with type B thymoma with stage III or IV.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 3","pages":"222-228"},"PeriodicalIF":4.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tumor-Infiltrating Lymphocytes (TILs) immunotherapy is a highly promising treatment for Non-small Cell Lung Cancer (NSCLC), which is responsible for 18% of all cancer-related deaths. The heterogeneity of TILs remains poorly understood. Here, we utilized combined single-cell RNA (scRNA)/T cell receptor sequencing (scTCR-seq) data from lung adenocarcinoma (LUAD) patients. Naïve CD4+ and effector memory CD8+ T cells were increased in tumor tissue compared with circulating blood samples. Activated signaling pathways were detected, and GZMA was identified as a potential novel diagnostic biomarker. During the transitional phase, macrophages (FTL) and dendritic (AIF1) cells transported the most CD3 TCR clones to T cells, while cytotoxicity CD8+ T (NKG7) cells transported to terminal exhausted CD8+ T cells. In both transition and expansion phases, T helper cells (CXCL13) are transported to regulatory T cells (Tregs). Additionally, we investigated the expression profiles of key cytokines, checkpoint receptors, and their ligands. Cytotoxicity CD8+ T cells (CCL5 and IFNG), T helper cells (FTL, TNFRSF4, and TIGIT), and regulatory T cells (CTLA4, TIGIT and FTL) exhibited functional roles in both primary and metastatic tumor stages. Taken together, our study provides a single-cell resolution of the TIL immune landscape and suggests potential treatment strategies to overcome drug resistance.
{"title":"Characterizing the immune landscape of tumor-infiltrating lymphocytes in non-small cell lung cancer","authors":"Jin-Guo Liu, Lin Yu, Xian-Ling Guo, Xue-Min He, Man Li, Ren-Yuan Gao, Bing-Hui Zhao, Qian-Yu Li, Wen-Jing Zhu, Ping Xu, Xiao-Hua Gu, Yong-An Chen, Xiao-Lan Yin, Yan Shang, Zhen-Hong Guo, Jia-Hao Mao, Yang-Xi Hu, Li-Ming Lu, Jian Hua, Hua Zhang, Yue Li","doi":"10.1038/s41435-025-00330-w","DOIUrl":"10.1038/s41435-025-00330-w","url":null,"abstract":"Tumor-Infiltrating Lymphocytes (TILs) immunotherapy is a highly promising treatment for Non-small Cell Lung Cancer (NSCLC), which is responsible for 18% of all cancer-related deaths. The heterogeneity of TILs remains poorly understood. Here, we utilized combined single-cell RNA (scRNA)/T cell receptor sequencing (scTCR-seq) data from lung adenocarcinoma (LUAD) patients. Naïve CD4+ and effector memory CD8+ T cells were increased in tumor tissue compared with circulating blood samples. Activated signaling pathways were detected, and GZMA was identified as a potential novel diagnostic biomarker. During the transitional phase, macrophages (FTL) and dendritic (AIF1) cells transported the most CD3 TCR clones to T cells, while cytotoxicity CD8+ T (NKG7) cells transported to terminal exhausted CD8+ T cells. In both transition and expansion phases, T helper cells (CXCL13) are transported to regulatory T cells (Tregs). Additionally, we investigated the expression profiles of key cytokines, checkpoint receptors, and their ligands. Cytotoxicity CD8+ T cells (CCL5 and IFNG), T helper cells (FTL, TNFRSF4, and TIGIT), and regulatory T cells (CTLA4, TIGIT and FTL) exhibited functional roles in both primary and metastatic tumor stages. Taken together, our study provides a single-cell resolution of the TIL immune landscape and suggests potential treatment strategies to overcome drug resistance.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 3","pages":"229-241"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-24DOI: 10.1038/s41435-025-00328-4
Stanley I. Letovsky, Xia Cao, Jill A. Hollenbach, Steven J. Mack, Martin Maiers
Genetic variation in the human leukocyte antigen (HLA) region is thought to influence susceptibility to and severity of a variety of infectious diseases. Several studies have explored a possible relationship between HLA genetics and SARS-CoV-2 infection, although mixed results, small sample sizes, and difficulty controlling for exposure risk have made it difficult to draw firm conclusions. Here, a dataset of 419,234 subjects with HLA genotype data and COVID-19 PCR test results was studied. A baseline analysis was performed to examine the association of non-HLA factors on COVID-19 positivity. Then, multivariate logistic regressions, incorporating single and paired HLA alleles, were performed and then corrected for significant factors from the baseline analysis. Proxies for socioeconomic status and exposure risk were significantly associated with COVID-19 positivity across all ancestry groups studied. Forty-one single HLA alleles displayed significant association with COVID-19 positivity; after controlling for socioeconomic status and exposure risk, only eight significant associations remained. Additionally, two HLA allele pairs were associated with test positivity after correction. Of all variables, socioeconomic status showed the greatest effect size. The results from this study suggest that many, if not all, of the reported associations between HLA alleles and SARS-CoV-2 infection may be spurious, owing to confounding factors.
{"title":"Association between HLA genetics and SARS-CoV-2 infection in a large real-world cohort","authors":"Stanley I. Letovsky, Xia Cao, Jill A. Hollenbach, Steven J. Mack, Martin Maiers","doi":"10.1038/s41435-025-00328-4","DOIUrl":"10.1038/s41435-025-00328-4","url":null,"abstract":"Genetic variation in the human leukocyte antigen (HLA) region is thought to influence susceptibility to and severity of a variety of infectious diseases. Several studies have explored a possible relationship between HLA genetics and SARS-CoV-2 infection, although mixed results, small sample sizes, and difficulty controlling for exposure risk have made it difficult to draw firm conclusions. Here, a dataset of 419,234 subjects with HLA genotype data and COVID-19 PCR test results was studied. A baseline analysis was performed to examine the association of non-HLA factors on COVID-19 positivity. Then, multivariate logistic regressions, incorporating single and paired HLA alleles, were performed and then corrected for significant factors from the baseline analysis. Proxies for socioeconomic status and exposure risk were significantly associated with COVID-19 positivity across all ancestry groups studied. Forty-one single HLA alleles displayed significant association with COVID-19 positivity; after controlling for socioeconomic status and exposure risk, only eight significant associations remained. Additionally, two HLA allele pairs were associated with test positivity after correction. Of all variables, socioeconomic status showed the greatest effect size. The results from this study suggest that many, if not all, of the reported associations between HLA alleles and SARS-CoV-2 infection may be spurious, owing to confounding factors.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 3","pages":"213-221"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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