Cancer letters最新文献

{"title":"Construction and validation of consensus clustering-derived metabolism- and immune-associated genes model for prognosis prediction in cancer patients with liver metastases","authors":"Jing Wu ,&nbsp;Xinyao Qiu ,&nbsp;Tao Zhou ,&nbsp;Yani Zhang ,&nbsp;Shuai Li ,&nbsp;Ji Hu ,&nbsp;Siyun Shen ,&nbsp;Lei Chen ,&nbsp;Yingcheng Yang ,&nbsp;Shuai Yang ,&nbsp;Hongyang Wang","doi":"10.1016/j.canlet.2025.217915","DOIUrl":"10.1016/j.canlet.2025.217915","url":null,"abstract":"<div><div>Liver metastasis (LM) is a cancer hallmark linked to poor prognosis and high mortality. Immune and metabolic shifts play critical roles in LM progression. This study aims to explore the prognostic value of immune- and metabolism-associated genes for LM and investigate their potential mechanisms. Here, we established a prognostic model based on Consensus Clustering-derived Metabolism- and Immune-associated genes (CCMI). Both the CCMI model and each hub gene demonstrated predictive value for LM patients at RNA and protein levels. Moreover, patients with high CCMI scores showed worse prognosis, elevated mutation frequency and heterogeneity, enrichment of cancer-promoting pathways, and increased neutrophil infiltration. Mechanistically, functional studies showed that CKB and ARG2 enhanced the proliferation, self-renewal, migration and invasion of cancer cells via activating MAPK or PI3K-AKT signaling pathways. MAFF was validated to play a key role in inducing neutrophil recruitment and infiltration through upregulating expression of CXCL1, thereby accelerating LM progression. In conclusion, this study presented a practical prognostic CCMI model for LM patients and investigated associated molecular and immune signatures. Our results uncovered the regulatory mechanisms of CCMI hub genes that promote LM progression, highlighting their potential as biomarkers for precision diagnosis and treatment of LM.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217915"},"PeriodicalIF":9.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623489","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":"The calcium homeostasis in tumor and the mechanism involving progression and metastasis","authors":"Zhenpu Qin ,&nbsp;Yuqin Di ,&nbsp;Tianrong Ma ,&nbsp;Wei Zeng ,&nbsp;Xianzhi Liu ,&nbsp;Weiling He","doi":"10.1016/j.canlet.2025.217908","DOIUrl":"10.1016/j.canlet.2025.217908","url":null,"abstract":"<div><div>Calcium ions (Ca²⁺) act as important intracellular second messengers and play a key role in cellular physiological functions and signal transduction. Ca²⁺ significantly affects the biological behavior of tumor cells by regulating mechanisms, such as cytoskeleton reorganization, cell migration, invasion, and immune escape. Although research on calcium homeostasis in tumor progression and metastasis was historically limited, it has recently received widespread attention. Growing evidence indicates that the disruption of calcium homeostasis is closely linked to the development, invasion, and metastasis of tumors. This paper systematically reviews the mechanisms governing calcium homeostasis in tumor progression and metastasis. We focused on calcium channels, pumps, and their regulatory roles in ionic signaling networks, the tumor microenvironment, downstream signaling pathways, and immune escape. We also discussed therapeutic strategies targeting tumor progression and metastasis via the modulation of calcium homeostasis. By elucidating the role of calcium homeostasis in tumor metastasis, this review aims to provide a theoretical foundation and to identify potential targets for novel anti-metastatic strategies.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217908"},"PeriodicalIF":9.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613868","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 fructose metabolism for cancer therapy","authors":"Qing Zhao ,&nbsp;Wen-Lian Chen ,&nbsp;Gerry Melino ,&nbsp;Wei Jia","doi":"10.1016/j.canlet.2025.217914","DOIUrl":"10.1016/j.canlet.2025.217914","url":null,"abstract":"<div><div>Cancer cells frequently rewire their metabolism to support rapid proliferation and invasion. Our analysis of the most lethal cancers in 2022 reveals a prominent association with dysregulated fructose metabolism. Fructose serves as a crucial alternative energy substrate under nutrient-deprived conditions, promoting the Warburg effect and thereby facilitating tumor growth and metastasis. Moreover, aberrant fructose utilization activates oncogenic mTORC1 signaling, suppresses anti-tumor immune responses, and facilitates tumor progression. Targeting key enzymes and transporters in fructose metabolism presents a promising therapeutic avenue to disrupt tumor bioenergetics and signaling pathways, potentially improving treatment efficacy and patient outcomes.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217914"},"PeriodicalIF":9.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623488","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":"Hypoxia and immunometabolism in the tumor microenvironment: insights into mechanisms and therapeutic potential","authors":"Cen Wu ,&nbsp;Tianhua Xu ,&nbsp;Heyang Zhang ,&nbsp;Yile Hu ,&nbsp;Jinghua Jiao ,&nbsp;Kun Qiu ,&nbsp;Jia Gu ,&nbsp;Wenya Li ,&nbsp;Lei Sun","doi":"10.1016/j.canlet.2025.217913","DOIUrl":"10.1016/j.canlet.2025.217913","url":null,"abstract":"<div><div>The tumor microenvironment (TME), regulated by both intrinsic oncogenic factors and immune metabolic processes, has become an increasing focus of research in recent years. Typical features of the TME include hypoxia, metabolic dysregulation, and immunosuppression. Metabolic reprogramming provides tumors with energy and biosynthetic compounds to meet the nutritional requirements for proliferation. Meanwhile, immune metabolism influences tumor cells to shape the tumor immunosuppressive microenvironment by altering immune cell function and phenotype. Tumor hypoxia signaling specifically fosters the development of immunosuppressive TME by regulating immune metabolism, which, in turn, supports the progression of malignant tumors through modulation of their biological behaviors. This review comprehensively explores the metabolic regulation of hypoxia and immune metabolism during the dynamic evolution of tumor-adapted TME. In the context of the intricate interplay between hypoxia and immunometabolism, the prospects and challenges associated with immunometabolism in the clinical management of tumors are systematically addressed.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217913"},"PeriodicalIF":9.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625327","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":"A noninvasive and highly efficient epigenetic predictive model for efficacy of the GOLP regimen in patients with intrahepatic cholangiocarcinoma","authors":"Xianlong Meng ,&nbsp;Jiacheng Lu ,&nbsp;Xiaoyong Huang ,&nbsp;Yixiang Shi ,&nbsp;Lei Yu ,&nbsp;Xiaojun Guo ,&nbsp;Pei Pu ,&nbsp;Zhiqiang Hu ,&nbsp;Shuyang Hu ,&nbsp;Mu Ye ,&nbsp;Xiaolong Cui ,&nbsp;Chen Liang ,&nbsp;Jiabin Cai ,&nbsp;Qiman Sun ,&nbsp;Yinghao Shen ,&nbsp;Qiang Gao ,&nbsp;Xiaolan Wang ,&nbsp;Chuan He ,&nbsp;Jian Zhou ,&nbsp;Jia Fan ,&nbsp;Guoming Shi","doi":"10.1016/j.canlet.2025.217911","DOIUrl":"10.1016/j.canlet.2025.217911","url":null,"abstract":"<div><div>The GOLP regimen (Gemcitabine, Oxaliplatin, Lenvatinib and anti-PD1 antibody) has been a promising first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA). A noninvasive tool to predict the response to GOLP regimen is needed for clinical practice. In this study, 188 cell-free DNA samples were collected before each cycle and after the third cycle (P0 to P3) from 47 iCCA patients receiving GOLP regimen. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles of samples were generated by 5hmC-Seal. Tumor response was assessed per Response Evaluation Criteria in Solid Tumors 1.1. Differential and functional analyses revealed that cell proliferation and malignancies associated pathways exhibited higher 5hmC level in poor responders at P1. Immune response related pathways presented higher 5hmC level in good responders at P2. Patients were split into training and validation cohorts by simple randomization at a ratio of 2:1 and a 5-features weighted predictive (wp-) model showing an area under the curve of 0.967 in the validation samples was constructed by machine learning. The model-derived wp-scores showed an opposite trend between good responders and poor responders from P0 to P3. In conclusion, our study identified novel epigenetic modifications and pathways across treatment process to reflect response to the GOLP regimen for iCCA patients. We developed a highly sensitive and specific 5hmC-based 5-features predictive model for GOLP treatment, holding the promise as a noninvasive tool for precision care of iCCA patients.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217911"},"PeriodicalIF":9.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613869","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":"Deglycosylated PD-L1 is a biomarker for immune checkpoint blockade response: a real-world study in breast cancer patients in Taiwan","authors":"Shao-Chun Wang ,&nbsp;Yi-Chun Shen ,&nbsp;Mei-Ren Pan ,&nbsp;Fu Ou-Yang ,&nbsp;Ting-Yi Liao ,&nbsp;Liang-Chih Liu ,&nbsp;Kun-Ming Rau ,&nbsp;Long-Sheng Lu ,&nbsp;Chi-Cheng Huang ,&nbsp;Ming-Shen Dai ,&nbsp;Yen-Shen Lu ,&nbsp;Hui-Wen Chang ,&nbsp;Han Chang ,&nbsp;Kai-Po Chang ,&nbsp;John Wang ,&nbsp;Chia-Jung Tsai ,&nbsp;I-Wen Chou ,&nbsp;Hong-Wei Li ,&nbsp;Wei-Chung Cheng ,&nbsp;Tsai-Chung Li ,&nbsp;Mien-Chie Hung","doi":"10.1016/j.canlet.2025.217912","DOIUrl":"10.1016/j.canlet.2025.217912","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is characterized by limited therapeutic options and a generally poor prognosis. Immune checkpoint blockade (ICB) therapies, particularly those targeting the PD-1/PD-L1 axis, offer promising treatment avenues, yet their effectiveness is contingent upon accurate assessment of PD-L1 expression. In this study, we collected 154 archived ICB-naïve TNBC tumor samples from multiple hospitals across Taiwan. We used immunohistochemistry (IHC) staining with the 28-8 monoclonal antibody to compare PD-L1 detection in samples treated with and without deglycosylation. Our findings revealed that under the standard IHC protocol without deglycosylation, 33.12 % of TNBC samples were classified as PD-L1 negative, which would have excluded these patients from ICB therapy eligibility. After deglycosylation, 84.31 % of the initially PD-L1-negative cases were reclassified as PD-L1 positive, indicating that glycosylation led to a 27.92 % false-negative rate in the TNBC samples. Notably, higher PD-L1 levels post-de-glycosylation were significantly associated with favorable responses to ICB treatments, particularly among patients receiving pembrolizumab and atezolizumab. Receiver operating characteristic (ROC) analysis demonstrated a stronger correlation between deglycosylated PD-L1 and treatment response, with an area under the curve (AUC) of 0.860, compared to 0.648 for non-deglycosylated PD-L1. These results underscore the clinical importance of deglycosylation in enhancing PD-L1 detection accuracy, enabling more precise patient selection for ICB therapies. Incorporating deglycosylation into PD-L1 assessment protocols may improve treatment outcomes for TNBC patients and establish deglycosylated PD-L1 as a more reliable biomarker for ICB therapy response.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217912"},"PeriodicalIF":9.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616327","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":"NCF2 drives tumor progression and metastasis through NR2F2/LATS2/YAP1 axis in esophageal squamous cell carcinoma","authors":"Huan Zhang ,&nbsp;Zhaokai Wang ,&nbsp;Naicheng Song ,&nbsp;Ang Xiao ,&nbsp;Yaxuan Liu ,&nbsp;Ai Huang ,&nbsp;Zuhuan Yao ,&nbsp;Zhihong Huang ,&nbsp;Quanchao Sun ,&nbsp;Yue Qu ,&nbsp;Shijie Xing ,&nbsp;Li Wan ,&nbsp;Qingfeng Zheng ,&nbsp;Lei Huang ,&nbsp;Ke Jiang","doi":"10.1016/j.canlet.2025.217902","DOIUrl":"10.1016/j.canlet.2025.217902","url":null,"abstract":"<div><div>The occurrence of lymph node spread is the major significant factor associated with esophageal squamous cell carcinoma (ESCC)'s poor prognosis, mainly because of its association with a high risk of recurrence after treatment. However, the biological mechanisms underlying lymphatic metastasis in ESCC are not well recognized. Here, we show that NCF2 is aberrantly overexpressed and is associated with poor prognosis in patients with ESCC. Dysregulation of NCF2 expression promotes ESCC progression and lymphatic metastasis in a ROS-independent manner. NCF2 directly interacts with NR2F2 and blocks its nuclear translocation, which can result in the downregulation of LATS2 and the activation of YAP1 and its target genes and thereby promote tumorigenesis, lymphangiogenesis and metastasis in ESCC. This study establishes that the NCF2/NR2F2/LATS2/YAP1 axis plays a vital role in tumorigenesis and metastasis, suggesting that NCF2 may serve as an attractive therapeutic target and prognostic marker in ESCC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217902"},"PeriodicalIF":9.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616328","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":"Autophagy paradox: Genetic and epigenetic control of autophagy in cancer progression","authors":"Chandra Sekhar Bhol ,&nbsp;Prakash Kumar Senapati ,&nbsp;Rakesh Kumar Kar ,&nbsp;Grace Chew ,&nbsp;Kewal Kumar Mahapatra ,&nbsp;E Hui Clarissa Lee ,&nbsp;Alan Prem Kumar ,&nbsp;Sujit Kumar Bhutia ,&nbsp;Gautam Sethi","doi":"10.1016/j.canlet.2025.217909","DOIUrl":"10.1016/j.canlet.2025.217909","url":null,"abstract":"<div><div>Autophagy is a highly regulated, evolutionarily conserved process of self-digestion controlled by autophagy-related (ATG) genes. It involves the lysosomal degradation of cargoes, including cytoplasmic organelles, misfolded proteins, and toxic aggregates, to enrich cellular nutrient pools and reduce oxidative stress. In normal cells, basal autophagy occurs to maintain cellular homeostasis, which changes during tumor initiation, progression, and malignant transformation. The alteration in autophagy in cancer remains unclear and under-explored. Research indicates that genetic regulations, such as gene mutations, gene polymorphisms, or epigenetic modifications, including DNA methylation, histone modification, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), regulate ATGs, orchestrating the fluctuating nature of autophagy in cancer. Many studies describe the paradoxical role of autophagy in cancer, portraying it as a double-edged sword depending on the context, oscillating between promoting cell survival and inducing cell death-the dual roles in preventing tumor initiation and supporting tumor progression place autophagy at the centre of controversy. Recent findings suggest that autophagy is regulated at the intrinsic cellular level and within the tumor microenvironment. Thus, identifying the molecules, mediators, and mechanisms associated with the regulation of autophagy during tumor development, maintenance, therapy resistance, and dormancy could open new research avenues to enhance the efficacy of cancer therapeutics. Furthermore, this review encompasses preclinical studies and clinical trials, highlighting the effectiveness of modulating autophagy in cancer therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217909"},"PeriodicalIF":9.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604288","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":"NF-κB-mediated cytokine secretion and glutamate metabolic reprogramming converge in breast cancer brain tropism","authors":"Sara Di Russo ,&nbsp;Giulia Elizabeth Borsatti ,&nbsp;Amani Bouzidi ,&nbsp;Francesca Romana Liberati ,&nbsp;Agnese Riva ,&nbsp;Farida Tripodi ,&nbsp;Lucrezia Romana Rolfi ,&nbsp;Sharon Spizzichino ,&nbsp;Antonella Tramutola ,&nbsp;Marzia Perluigi ,&nbsp;Daniela Trisciuoglio ,&nbsp;Giorgio Giardina ,&nbsp;Alessandro Paiardini ,&nbsp;Paola Coccetti ,&nbsp;Serena Rinaldo ,&nbsp;Francesca Cutruzzolà ,&nbsp;Alessio Paone","doi":"10.1016/j.canlet.2025.217907","DOIUrl":"10.1016/j.canlet.2025.217907","url":null,"abstract":"<div><div>Brain metastases are an increasingly common and life-threatening complication of breast cancer. Here, we report that breast cancer cells with a propensity for cerebral colonization (BrM cells) display a distinct imbalance in the NF-κB pathway characterized by elevated IKKβ and reduced IKKα levels. This imbalance reduces the levels of the downstream NF-κB modulators IκBα and TAX1BP1, fostering a chronically active pro-inflammatory program. Such BrM cells secrete high concentrations of IL-8 and GRO chemokines, enhancing blood–brain barrier permeability <em>in vitro</em> and triggering astrocyte activation <em>in vivo</em>. In parallel, we observed that the altered NF-κB signaling increases the expression of glutamate transporters EAAT1 and EAAT2, which allows BrM cells to uptake and utilize glutamate, a neurotransmitter readily available in the brain, as a key energy source. Analysis of energy metabolism confirms a pronounced reliance on glutamate for both oxidative phosphorylation and glycolysis, which correlates with an increased migratory and invasive capacity. Importantly, pharmacological inhibition of glutamate import curtails <em>in vitro</em> migratory ability and reduces the formation of brain lesions in a murine model.</div><div>Our study thus highlights a dual strategy employed by BrM cells, whereby they orchestrate a pro-inflammatory milieu to breach the BBB and simultaneously exploit glutamate metabolism to sustain invasiveness. These findings highlight the inflammatory–metabolic axis as a promising target for therapeutic or preventive strategies against breast cancer progression to the brain.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217907"},"PeriodicalIF":9.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596920","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":"Preserved host immunity with intercellular adhesion molecule-1 (ICAM-1)-targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of triple-negative breast cancer and other malignancies","authors":"Seiichiro Takao,&nbsp;Hideyuki Furumoto,&nbsp;Aki Furusawa,&nbsp;Makoto Kano,&nbsp;Hiroshi Yamamoto,&nbsp;Motofumi Suzuki,&nbsp;Miyu Kano,&nbsp;Peter L. Choyke,&nbsp;Hisataka Kobayashi","doi":"10.1016/j.canlet.2025.217906","DOIUrl":"10.1016/j.canlet.2025.217906","url":null,"abstract":"<div><div>Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that combines an antibody photoabsorber-conjugate (APC) with NIR light to induce direct cytotoxicity and immunogenic cell death. Intercellular Adhesion Molecule 1 (ICAM-1), a cell surface protein overexpressed in various cancers, is a promising target for cancer therapy. We previously reported that ICAM-1-targeted NIR-PIT could be used in the treatment of ICAM-1 expressing triple-negative breast cancer (TNBC); however, ICAM-1 is also expressed on immune cells within the tumor microenvironment (TME). Therefore, the net impact of ICAM-1-targeted NIR-PIT on the tumor vs. antitumor host immunity remains unclear, posing a significant challenge to its clinical advancement. In this study, we investigated the antitumor effect of ICAM-1-targeted NIR-PIT including its influence on host immunity following NIR light irradiation, using immunocompetent mouse models. In vitro, ICAM-1-targeted NIR-PIT caused immunogenic cell death in EO771 (breast cancer) and SP2/0 (myeloma) models expressing ICAM-1. Ex vivo, ICAM-1-targeted NIR-PIT effectively eliminated ICAM-1-expressing cancer cells and immune cells within the TME. However, the net effect was to suppress tumor progression and prolong survival in EO771, MOC1 (oral carcinoma), and SP2/0 models in vivo. Enhanced antitumor host immunity was observed after ICAM-1-targeted NIR-PIT in the MOC1 model. In conclusion, ICAM-1-targeted NIR-PIT holds promise as a treatment for various cancer models expressing ICAM-1 beyond TNBC by directly killing cancer cells and enhancing host immune response.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217906"},"PeriodicalIF":9.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596919","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}