{"title":"Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients.","authors":"Tzu-Chun Cheng, Mien-Chie Hung, Lu-Hai Wang, Shih-Hsin Tu, Chih-Hsiung Wu, Yun Yen, Chi-Long Chen, Jacqueline Whang-Peng, Wen-Jui Lee, You-Cheng Liao, Yu-Ching Lee, Min-Hsiung Pan, Hui-Kuan Lin, Huey-En Tzeng, Peixuan Guo, Cheng-Ying Chu, Li-Ching Chen, Yuan-Soon Ho","doi":"10.1186/s40364-024-00715-5","DOIUrl":"10.1186/s40364-024-00715-5","url":null,"abstract":"<p><strong>Background: </strong>Up to 23% of breast cancer patients recurred within a decade after trastuzumab treatment. Conversely, one trial found that patients with low HER2 expression and metastatic breast cancer had a positive response to trastuzumab-deruxtecan (T-Dxd). This indicates that relying solely on HER2 as a single diagnostic marker to predict the efficacy of anti-HER2 drugs is insufficient. This study highlights the interaction between histamine N-methyltransferase (HNMT) and HER2 as an adjunct predictor for trastuzumab response. Furthermore, modulation of HER2 expression by HNMT may explain why those with low HER2 expression still respond to T-Dxd.</p><p><strong>Methods: </strong>We investigated the impact of HNMT protein expression on the efficacy of anti-HER2 therapy in both in vivo and ex vivo models of patient-derived xenografts and cell line-derived xenografts. Our analysis included Förster resonance energy transfer (FRET) to assess the interaction strength between HNMT and HER2 proteins in trastuzumab-resistant and sensitive tumor tissues. Additionally, we used fluorescence lifetime imaging microscopy (FLIM), cleaved luciferase, and immunoprecipitation to study the interaction dynamics of HNMT and HER2. Furthermore, we evaluated the influence of HNMT activity on the binding of anti-HER2 antibodies to their targets through flow cytometry. We also observed the nuclear translocation of HNMT/HER2-ICD cells using fluorescent double staining and DeltaVision microscopy. Finally, ChIP sequencing was employed to identify target genes affected by the HNMT/HER2-ICD complex.</p><p><strong>Results: </strong>This study highlights HNMT as a potential auxiliary biomarker for diagnosing HER2 + breast cancer. FRET analysis demonstrated a significant interaction between HNMT and HER2 protein in trastuzumab-sensitive tumor tissue (n = 50), suggesting the potential of HNMT as a predictor of treatment response. Mechanistic studies revealed that the interaction between HNMT and HER2 contributes to increased HER2 protein expression at the transcriptional level, thereby impacting the efficacy of anti-HER2 therapy. Furthermore, a subset of triple-negative breast cancers characterized by HNMT overexpression was found to be sensitive to HER2 antibody-drug conjugates such as T-Dxd.</p><p><strong>Conclusions: </strong>These findings offer crucial insights for clinicians evaluating candidates for anti-HER2 therapy, especially for HER2-low breast cancer patients who could gain from T-Dxd treatment. Identifying HNMT expression could help clinicians pinpoint patients who would benefit from anti-HER2 therapy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"7"},"PeriodicalIF":9.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958499","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}
Fanghui Chen, Liwei Lang, Jianqiang Yang, Fan Yang, Sijia Tang, Zhenzhen Fu, Nabil F Saba, Ming Luo, Yong Teng
{"title":"SMAC-armed oncolytic virotherapy enhances the anticancer activity of PD1 blockade by modulating PANoptosis.","authors":"Fanghui Chen, Liwei Lang, Jianqiang Yang, Fan Yang, Sijia Tang, Zhenzhen Fu, Nabil F Saba, Ming Luo, Yong Teng","doi":"10.1186/s40364-025-00726-w","DOIUrl":"10.1186/s40364-025-00726-w","url":null,"abstract":"<p><strong>Background: </strong>Oncolytic viruses (OVs) are increasingly recognized as promising tools for cancer therapy, as they selectively infect and destroy tumor cells while leaving healthy cells unharmed. Despite considerable progress, the limited therapeutic efficacy of OV-based virotherapy continues to be a significant challenge in cancer treatment.</p><p><strong>Methods: </strong>The SMAC/DIABLO gene was inserted into the genome of vesicular stomatitis virus (VSV) to generate VSV-S. Head and neck squamous cell carcinoma (HNSCC) cell lines and orthotopic mouse models were employed for research. Morphological changes were observed using both light microscopy and transmission electron microscopy. Molecular alterations were analyzed through Western blotting and ELISA kits. The tumor secretome was characterized using a combination of biotinylation and LC-MS analysis. Immune cell changes were evaluated by flow cytometry and immunohistochemistry.</p><p><strong>Results: </strong>Compared to its parental virus, VSV-S not only increases apoptosis by overexpressing SMAC during VSV infection but also triggers elevated levels of PANoptosis (pyroptosis, apoptosis, and necroptosis) in HNSCC cells via activation of caspase-1/gasdermin D (GSDMD) signaling. As a result, VSV-S-induced PANoptosis promotes CD8<sup>+</sup> T cell tumor infiltration and enhances their cytotoxic capacity, eventually potentiating T cell-mediated antitumor immunity. Moreover, VSV-S reduces PDL1 levels in HNSCC cells and, in combination with PD1 blockade, produces a more potent antitumor effect than either therapy alone.</p><p><strong>Conclusions: </strong>Our findings demonstrate that the combination of VSV-S and PD1 blockade offers a synergistic therapeutic strategy for HNSCC, supporting the advancement of VSV-based virotherapy as a promising strategy to improve outcomes for HNSCC patients.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"8"},"PeriodicalIF":9.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958522","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}
Lemchukwu C Amaeshi, Amalia A Sofianidi, Aditi Shastri, Mendel Goldfinger, Marina Konopleva, Amit K Verma, Mark Chaitowitz, Ioannis Mantzaris
{"title":"A germline FLT3 variant in aplastic anemia.","authors":"Lemchukwu C Amaeshi, Amalia A Sofianidi, Aditi Shastri, Mendel Goldfinger, Marina Konopleva, Amit K Verma, Mark Chaitowitz, Ioannis Mantzaris","doi":"10.1186/s40364-024-00717-3","DOIUrl":"https://doi.org/10.1186/s40364-024-00717-3","url":null,"abstract":"<p><p>FMS-like tyrosine kinase 3 (FLT3) genetic variants are commonly seen in high-grade myeloid neoplasms and are typically gain-of-function mutations associated with a proliferative disease phenotype. Inactivating FLT3 variants have been less frequently described in non-malignant, autoimmune disorders and are uncommon in aplastic anemia (AA). Herein, we report the first to our knowledge, and unusual case of a germline, gain-of-function, FLT3 variant in a patient with severe AA treated successfully with immunosuppressive therapy. Although a proposed link between dysregulated FLT3 signaling and autoimmunity has been described and could be speculated in the case of AA, it is currently unknown whether a pathogenetic connection between an activating germline FLT3 variant and AA truly exists and whether the mutation signifies a lifelong risk of disease recurrence and/or clonal evolution. However, the recognition of the FLT3 gene as subject not only to somatic but also germline mutations is the first step in interrogating its functional implications. Further study of unusual genotype-phenotype combinations, such as in the case presented, may shed light on a potential pathogenetic link.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"4"},"PeriodicalIF":9.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958916","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}
Niping Qin, Yangyan Fan, Tao Yang, Zhiping Yang, Daiming Fan
{"title":"The burden of Gastric Cancer and possible risk factors from 1990 to 2021, and projections until 2035: findings from the Global Burden of Disease Study 2021.","authors":"Niping Qin, Yangyan Fan, Tao Yang, Zhiping Yang, Daiming Fan","doi":"10.1186/s40364-024-00720-8","DOIUrl":"https://doi.org/10.1186/s40364-024-00720-8","url":null,"abstract":"<p><strong>Background and objective: </strong>Gastric cancer (GC) remains a significant global health challenge, characterized by high incidence and mortality rates, particularly in East Asia. A comprehensive understanding of the disease burden of gastric cancer is crucial for developing effective prevention and treatment strategies. However, comprehensive global assessments of the disease burden of gastric cancer remain limited. This study, based on the Global Burden of Disease (GBD) framework, systematically analyzes global trends in gastric cancer from 1990 to 2021 and projects future trends through 2035, aiming to provide scientific evidence for policymaking.</p><p><strong>Methods: </strong>The data were derived from the Global Burden of Disease (GBD) Study 2021, covering gastric cancer (GC) incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs), and age-standardized DALY rates (ASRs) across 204 countries and regions from 1990 to 2021. The Bayesian age-period-cohort model was employed to project trends up to 2035.</p><p><strong>Results: </strong>In comparison with 1990, both the incidence and mortality of GC rose in 2021, with over 1.23 million new cases recorded globally, resulting in 954,373.60 deaths and 22,786,633.10 DALYs. Between 1990 and 2021, the ASIRs, ASDRs, and ASRs decreased by 42% (ranging from 49 to 35%), 49% (ranging from 55 to 43%), and 53% (ranging from 58 to 47%), respectively. The peak ASIRs and ASDRs in 2021 were seen in the high-middle SDI quintile. Males exhibited higher rates of ASDRs, ASIRs, and ASRs compared to females. In 2021, East Asia and high-income North America bore the largest burden of smoking-related GC, while Central Europe experienced the highest burden from high-sodium diets. Forecasts toward 2035 indicate a continued decline in both ASIRs and ASDRs.</p><p><strong>Conclusions: </strong>Despite notable reductions in both incidence and mortality, GC remains a substantial global burden, affecting various regions and countries. Deaths and DALYs related to high-sodium diets and smoking have shown an overall decline. However, substantial regional and age-related disparities persist. Targeted interventions, such as smoking control and promoting the intake of fresh fruits and vegetables, are essential in diminishing GC risk.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"5"},"PeriodicalIF":9.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958652","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}
Ji U Choi, Yeongrin Kim, Da Yeon Lee, Jin Song Park, Moonjung Jeun, Heung Kyoung Lee, Chi Hoon Park
{"title":"Lentivirus-based production of human chimeric antigen receptor macrophages from peripheral blood.","authors":"Ji U Choi, Yeongrin Kim, Da Yeon Lee, Jin Song Park, Moonjung Jeun, Heung Kyoung Lee, Chi Hoon Park","doi":"10.1186/s40364-024-00703-9","DOIUrl":"10.1186/s40364-024-00703-9","url":null,"abstract":"<p><p>Although chimeric antigen receptor (CAR) T cell therapy has shown remarkable efficacy against leukemic cells, it still has critical limitations. CAR macrophage has been regarded as a potential alternative to CAR T cells. However, due to the difficulties in gene transduction into macrophages, the production of primary human CAR macrophages from peripheral blood mononuclear cells (PBMC) using lentivirus is highly challenging. Here, we report on how to generate CAR macrophages from human PBMC with lentiviral particles. Using our lentiviral protocol, we produced functional CAR macrophages to lyse and phagocytose target cancer cells efficiently.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"1"},"PeriodicalIF":9.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924062","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":"A machine learning-based model to predict POD24 in follicular lymphoma: a study by the Chinese workshop on follicular lymphoma.","authors":"Jie Zha, Qinwei Chen, Wei Zhang, Hongmei Jing, Jingjing Ye, Huanhuan Liu, Haifeng Yu, Shuhua Yi, Caixia Li, Zhong Zheng, Wei Xu, Zhifeng Li, Zhijuan Lin, Lingyan Ping, Xiaohua He, Liling Zhang, Ying Xie, Feili Chen, Xiuhua Sun, Liping Su, Huilai Zhang, Haiyan Yang, Weili Zhao, Lugui Qiu, Zhiming Li, Yuqin Song, Bing Xu","doi":"10.1186/s40364-024-00716-4","DOIUrl":"https://doi.org/10.1186/s40364-024-00716-4","url":null,"abstract":"<p><strong>Background: </strong>Disease progression within 24 months (POD24) significantly impacts overall survival (OS) in patients with follicular lymphoma (FL). This study aimed to develop a robust predictive model, FLIPI-C, using a machine learning approach to identify FL patients at high risk of POD24.</p><p><strong>Methods: </strong>A cohort of 1,938 FL patients (FL1-3a) from seventeen centers nationwide in China was randomly divided into training and internal validation sets (2:1 ratio). XGBoost was utilized to construct the POD24-predicting model, which was internally validated in the validation set and externally validated in the GALLIUM cohort. Key predictors of POD24 included lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) > ULN, low hemoglobin (Hb), elevated beta-2 microglobulin (β2-MG), maximum standardized uptake value (SUVmax), and lymph node involvement. The FLIPI-C model assigned 2 points to LMR and 1 point to each of the other variables.</p><p><strong>Results: </strong>The FLIPI-C model demonstrated superior accuracy (AUC) for predicting POD24 and 3-year overall survival (OS) in both the internal (AUC POD24: 0.764, OS: 0.700) and external validation cohorts (AUC POD24: 0.703, OS: 0.653), compared to existing models (FLIPI, FLIPI-2, PRIMA-PI, FLEX). Decision curve analysis confirmed the superior net benefits of FLIPI-C.</p><p><strong>Conclusions: </strong>Developed using a machine learning approach, the FLIPI-C model offers superior predictive accuracy and utilizes simple, widely available markers. It holds promise for informing treatment decisions and prognostic assessments in clinical practice for FL patients at high risk of POD24.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"2"},"PeriodicalIF":9.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928618","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}
Kexin Zhao, Yangqing Sun, Shangwei Zhong, Jun-Li Luo
{"title":"The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.","authors":"Kexin Zhao, Yangqing Sun, Shangwei Zhong, Jun-Li Luo","doi":"10.1186/s40364-024-00711-9","DOIUrl":"10.1186/s40364-024-00711-9","url":null,"abstract":"<p><p>The cathepsin family comprises lysosomal proteases that play essential roles in various physiological processes, including protein degradation, antigen presentation, apoptosis, and tissue remodeling. Dysregulation of cathepsin activity has been linked to a variety of pathological conditions, such as cancer, autoimmune diseases, and neurodegenerative disorders. Understanding the functions of cathepsins is crucial for gaining insights into their roles in both health and disease, as well as for developing targeted therapeutic approaches. Emerging research underscores the significant involvement of cathepsins in immune cells, particularly T cells, macrophages, dendritic cells, and neutrophils, as well as their contribution to immune-related diseases. In this review, we systematically examine the impact of cathepsins on the immune system and their mechanistic roles in cancer, infectious diseases, autoimmune and neurodegenerative disorders, with the goal of identifying novel therapeutic strategies for these conditions.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"165"},"PeriodicalIF":9.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907960","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":"PCSK9 in T-cell function and the immune response.","authors":"Yuying Wang, Xiaosheng Fang, Jiarui Liu, Xiao Lv, Kang Lu, Yingxue Lu, Yujie Jiang","doi":"10.1186/s40364-024-00712-8","DOIUrl":"10.1186/s40364-024-00712-8","url":null,"abstract":"<p><p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) was first reported in 2003 and confirmed to be strongly associated with familial hypercholesterolemia. Small-molecule inhibitors targeting PCSK9 provide an effective and safe method for managing hypercholesterolemia and reducing the cardiovascular risk. In recent years, increasing evidence has indicated other important roles for PCSK9 in inflammation, tumors, and even immune regulation. PCSK9 might be an attractive regulator of T-cell activation and expansion. It might mediate inflammation and regulate other types of immune cells. In this review, we summarize the current advances in the field of PCSK9 and provide a narrative of the biological processes associated with PCSK9. The relationships between PCSK9 and different T cells were investigated in depth. Finally, the signaling pathways associated with PCSK9 and the immune response are also summarized in this review.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"163"},"PeriodicalIF":9.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907954","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":"Platelet signaling in immune landscape: comprehensive mechanism and clinical therapy.","authors":"Mengyao Yan, Zhe Wang, Zhiwei Qiu, Yimin Cui, Qian Xiang","doi":"10.1186/s40364-024-00700-y","DOIUrl":"10.1186/s40364-024-00700-y","url":null,"abstract":"<p><p>Platelets are essential for blood clotting and maintaining normal hemostasis. In pathological conditions, platelets are increasingly recognized as crucial regulatory factors in various immune-mediated inflammatory diseases. Resting platelets are induced by various factors such as immune complexes through Fc receptors, platelet-targeting autoantibodies and other platelet-activating stimuli. Platelet activation in immunological processes involves the release of immune activation stimuli, antigen presentation and interaction with immune cells. Platelets participate in both the innate immune system (neutrophils, monocytes/macrophages, dendritic cells (DCs) and Natural Killer (NK) cells and the adaptive immune system (T and B cells). Clinical therapeutic strategies include targeting platelet activation, platelet-immune cell interaction and platelet-endothelial cell interaction, which display positive development prospects. Understanding the mechanisms of platelets in immunity is important, and developing targeted modulations of these mechanisms will pave the way for promising therapeutic strategies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"164"},"PeriodicalIF":9.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907956","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":"Tumor microenvironment and immunotherapy for triple-negative breast cancer.","authors":"Zijie Guo, Ziyu Zhu, Xixi Lin, Shenkangle Wang, Yihong Wen, Linbo Wang, Lili Zhi, Jichun Zhou","doi":"10.1186/s40364-024-00714-6","DOIUrl":"10.1186/s40364-024-00714-6","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a subtype of breast cancer known for its high aggressiveness and poor prognosis. Conventional treatment of TNBC is challenging due to its heterogeneity and lack of clear targets. Recent advancements in immunotherapy have shown promise in treating TNBC, with immune checkpoint therapy playing a significant role in comprehensive treatment plans. The tumor microenvironment (TME), comprising immune cells, stromal cells, and various cytokines, plays a crucial role in TNBC progression and response to immunotherapy. The high presence of tumor-infiltrating lymphocytes and immune checkpoint proteins in TNBC indicates the potential of immunotherapeutic strategies. However, the complexity of the TME, while offering therapeutic targets, requires further exploration of its multiple roles in immunotherapy. In this review, we discuss the interaction mechanism between TME and TNBC immunotherapy based on the characteristics and composition of TME, and elaborate on and analyze the effect of TME on immunotherapy, the potential of TME as an immune target, and the ability of TME as a biomarker. Understanding these dynamics will offer new insights for enhancing therapeutic approaches and investigating stratification and prognostic markers for TNBC patients.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"166"},"PeriodicalIF":9.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11689763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911082","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}