BMC Cancer最新文献

{"title":"Impact of unmet needs on health-related quality of life among cancer survivors in Ulsan, Korea.","authors":"Dong Yeop Lee, Cheolkyung Sin, Minsu Ock, Hyeyeong Kim, Hyeon-Su Im, Youjin Kim, Su-Jin Koh, Dong Yoon Kang","doi":"10.1186/s12885-026-15968-6","DOIUrl":"https://doi.org/10.1186/s12885-026-15968-6","url":null,"abstract":"<p><strong>Background: </strong>Cancer survivorship care emphasizes biomedical interventions, but psychological and social difficulties remain underaddressed. This study aimed to (i) quantify the association between unmet needs and quality of life (QOL), and (ii) evaluate whether these associations are consistent across two health-related QOL (HRQoL) instruments among cancer survivors.</p><p><strong>Methods: </strong>Cross-sectional survey of adults (≥ 19) in Ulsan, Korea (2021, 2022). HRQoL (EQ-5D-5 L; EORTC QLQ-C30) was related to unmet-need domains using multivariable linear regression adjusted for prespecified sociodemographic and clinical covariates (gender, age, cancer type/stage, education level, household size, household monthly income, smoking status, alcohol consumption). Statistical analyses included Student's t-tests, one-way ANOVA, and multivariable linear regression.</p><p><strong>Results: </strong>After excluding cases with insufficient information, 372 survivors were analyzed. EQ-5D-5 L utility was negatively associated with age ≥ 60 years (B=-0.04, 95%CI[-0.07, -0.01]), advanced cancer stage (Stage IV: B=-0.11, 95%CI[-0.14, -0.07]), unmet psychological needs (B=-0.09, 95%CI[-0.13, -0.06]), and unmet financial needs (B=-0.04, 95%CI[-0.09, -0.001]). On the EORTC QLQ-C30, advanced cancer stage showed negative associations with the functional scale (Stage IV: B=-14.87, 95%CI[-18.65, -11.10]) and positive associations with the symptom scale (Stage IV: B = 9.01, 95%CI[6.44, 11.57]). Higher household income (B = 4.99, 95%CI[1.71, 8.26]) was positively associated with the functional scale, while unmet psychological needs were negatively associated with the functional scale (B=-5.96, 95%CI[-10.04, -1.89]) and positively associated with the symptom scale (B = 8.80, 95%CI[6.04, 11.57]).</p><p><strong>Conclusions: </strong>Unmet psychological needs showed the most consistent associations with poorer HRQoL across both generic and cancer-specific instruments. Unmet financial needs showed weaker but directionally consistent associations, and the concurrent use of both instruments provided complementary perspectives on survivorship-related quality of life.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel Chimeric Antigen Receptor (CAR) - strategy to target EGFR^VIII-mutated glioblastoma cells via macrophages.","authors":"Kristi Vera, Gülen Esken, Jin Wook Hwang, Carine Elbaz, Diana Chaker, Noufissa Oudrhiri, Christophe Desterke, Frank Griscelli, Annelise Bennaceur-Griscelli, Ali G Turhan","doi":"10.1186/s12885-026-16080-5","DOIUrl":"https://doi.org/10.1186/s12885-026-16080-5","url":null,"abstract":"<p><strong>Background: </strong>Autologous chimeric antigen receptor (CAR) expressing T-Cells (CAR-T) have been efficiently used in hematological malignancies but their efficacy in solid tumors remains limited. CAR therapies via the use of macrophages, offer a promising avenue due to their unique ability to infiltrate tumors and to initiate phagocytosis.</p><p><strong>Methods: </strong>To generate a preclinical model of CAR-Macs, we have designed a novel CAR-construct to target EGFR^VIII-expressing glioblastoma cells (DK-MG) using THP-1 monocytic cell line able to differentiate towards macrophages. The CAR structure comprises a ScFv recognizing specifically EGFR^VIII and MEGF10 intracellular domain which enhances tethering and phagocytosis activity.</p><p><strong>Results: </strong>THP-1 cell line expressing CAR and control constructs were generated via lentiviral transduction followed by generation of monocytes and CAR-expressing M1 macrophages (CAR-Macs). To evaluate their ability of phagocytosis, we co-cultured THP-1 derived WT macrophages or CAR-Macs in the presence of target DK-MG cells. Confocal microscopy experiments revealed highly efficient phagocytosis of DK-MG EGFR^VIII cells by CAR-Macs (~ 60%) as compared to WT cells (~ 15%). The killing potential of the anti-EGFR^VIII CAR-Macs against the glioblastoma cell line has also been observed using video microscopy. ELISA and LDH assays performed in co-culture supernatants, showed an increase of IL-6 and LDH levels suggesting efficient cytotoxicity via CAR-Macs. Transcriptome analyses performed in purified CAR-Macs, revealed evidence of a molecular signature in favor of successful phagocytosis.</p><p><strong>Conclusions: </strong>The model described in this work is suitable for allowing translation to iPSC-derived macrophages to generate clinically applicable future cell therapy approaches in solid tumors expressing mutated variant EGFR^VIII.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking metabolic signature modifies the risk of colorectal cancer and interacts with genetic susceptibility: a large-scale prospective cohort study.","authors":"Jing Wang, Jiawei Zhang, Zhuoyi Wu, Yuqiang Zhao, Shiyin Meng, Wenjie Xuan, Jing Ni","doi":"10.1186/s12885-026-16123-x","DOIUrl":"https://doi.org/10.1186/s12885-026-16123-x","url":null,"abstract":"<p><strong>Background: </strong>Smoking tobacco is proven to be associated with higher colorectal cancer (CRC) risk. However, the metabolic pathways of smoking and how they relate to CRC risk are unclear.</p><p><strong>Methods: </strong>A total of 227,898 participants from the UK Biobank were included. A two-stage strategy with a combination of linear regression and Mendelian randomization analysis was employed to identify smoking-related metabolites. Then the elastic net (EN) regression model was used to construct smoking-related metabolic signature. Multivariable Cox regression, Mediation analysis, and interaction analysis were employed to illustrate the associations of smoking and smoking related metabolic signature on the risk of CRC. Furthermore, the interaction between genetic susceptibility and smoking metabolic signature was estimated based on relative excess risk due to interaction (RERI) and multiplicative-scale interaction.</p><p><strong>Results: </strong>During a follow-up of 12.5 years, 3,328 incident CRC patients were observed. We identified 71 smoking-related metabolites and screened 42 of them metabolites by EN model to construct smoking-related metabolic signature. We observed smoking and smoking metabolic signature were both associated with the elevated risk of CRC, with a hazard ratio (HR) value of 1.27 and 1.38, respectively. Mediation analysis revealed metabolic signature can mediate 10.03% in the association between smoking and CRC risk. The additive interaction between genetic susceptibility and metabolic signature was statistically significant (RERI = 0.70, 95% confidence interval [CI] = 0.29-1.10).</p><p><strong>Conclusion: </strong>The detrimental impact of smoking on CRC risk is mediated partially by smoking metabolic signature, which is synergistic with genetic susceptibility.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experiences accessing and receiving tumour genetic profiling in Victoria: a consumer-led cross-sectional survey study.","authors":"","doi":"10.1186/s12885-026-16052-9","DOIUrl":"https://doi.org/10.1186/s12885-026-16052-9","url":null,"abstract":"<p><strong>Background: </strong>Tumour genetic profiling has the potential to significantly improve cancer care by informing targeted treatments and improving patient outcomes. As use increases worldwide, greater attention should be paid to consumer experiences, need and priorities. This study is consumer-led and aims to inform an equitable and ethical roll out of future services by exploring consumer: 1) awareness of tumour genetic profiling, 2) experiences with tumour genetic profiling, and 3) priorities for improving access to and delivery of tumour genetic profiling within Victoria, Australia.</p><p><strong>Methods: </strong>A consumer reference group was formed and supported by experienced researchers and professional staff of a comprehensive cancer centre alliance to develop and conduct the research study. A cross-sectional survey was conducted between January and May 2024, capturing demographic and disease characteristics, along with questions relating to each aim. Both quantitative and qualitative data were collected. Eligible participants were patients diagnosed with cancer whose treatment teams were based in Victoria, Australia, or caregivers of such patients.</p><p><strong>Results: </strong>Of the 181 respondents (n = 36 carers, n = 145 patients), 23% (n = 44) reported that they (or the person they cared for) had undergone tumour genetic profiling. The majority reported a positive impact, including increased knowledge/understanding (n = 30, 68%) and personalised treatment options (n = 23, 52%), with very low decisional regret (mean: 3/100). However, 14% reported no understanding of the results at all, and confusion was reported as a drawback of testing. Higher education and greater shared decision making were associated with better understanding of results (p = 0.02 and p = 0.04, respectively) and higher education was also associated with greater awareness of genetic tumour profiling (p = 0.008). The primary barriers to uptake were lack of awareness (n = 88, 83%) and lack of perceived benefit from the treatment team (n = 19, 18%). Key strategies for improvement identified by participants included government-subsidised testing and improved patient and clinician education.</p><p><strong>Conclusions: </strong>This study highlighted gaps in consumer awareness and access to tumour genetic profiling, as well as the benefits of shared decision making. Overall, consumer-led insights emphasise the need for equitable funding, education, and systemic improvements. These findings can inform policies and practices aimed at delivering person-centred cancer care in Victoria and beyond. Future longitudinal research is needed to comprehensively explore these associations and track progress.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR4-high expression is associated with an immune-responsive phenotype in HCC and predicts inferior efficacy of lenvatinib plus PD-1 blockade.","authors":"Fuqun Wei, Weifu Liu, Zhisheng Chen, Zhongwu Chen, Jingfeng Liu","doi":"10.1186/s12885-026-16098-9","DOIUrl":"https://doi.org/10.1186/s12885-026-16098-9","url":null,"abstract":"<p><strong>Background: </strong>The LEAP-002 study showed that pembrolizumab plus lenvatinib did not provide statistically significant prognostic improvement over lenvatinib monotherapy in advanced hepatocellular carcinoma (HCC). This study investigated the potential protective role of high fibroblast growth factor receptor 4 (FGFR4) expression, a therapeutic target of lenvatinib, in immunotherapy for HCC.</p><p><strong>Methods: </strong>The Kaplan Meier plotter database was used to assess the impact of FGFR4 expression on immunotherapy outcomes; the TCGA-LIHC dataset was analyzed for correlations between FGFR4 expression, immune checkpoint gene profiles, and immune cell infiltration; and single-cell RNA sequencing (scRNA-seq) data from GSE149614 were used to examine interactions between high- and low-FGFR4 cancer cell subpopulations and immune cells. Validation was performed in tumor specimens from HCC patients treated with lenvatinib in combination with PD-1 inhibitors.</p><p><strong>Results: </strong>High FGFR4 expression predicted favorable immunotherapy outcomes and correlated with immune checkpoint genes such as PCDH1 and CD274, along with reduced M2 macrophage infiltration in TCGA-LIHC. scRNA-seq analysis showed FGFR4 enrichment in cancer cells, with high-FGFR4 cancer cells displaying a unique CXCL1-CXCR2 signaling axis with macrophages. High FGFR4 expression activated the MAPK pathway and increased JUN(+) transcriptional activity, showing a significant positive correlation with CXCL1 levels. In HCC patients treated with lenvatinib plus PD-1 inhibitors, high FGFR4 expression was linked to enhanced M1 macrophage polarization and elevated PD-L1 expression, whereas low FGFR4 expression correlated with better clinical outcomes.</p><p><strong>Conclusion: </strong>FGFR4-high expression is associated with an immune-responsive phenotype in HCC and predicts inferior efficacy of lenvatinib plus PD-1 blockade.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe anemia as a risk factor in Japanese patients with ovarian cancer receiving olaparib: a retrospective study.","authors":"Kenta Yamaoka, Manabu Kume, Ayako Matsumoto, Masaki Hirabatake, Nobutaka Hayashi, Tadashi Shimizu, Takuya Aoki, Nobuyuki Muroi","doi":"10.1186/s12885-026-16148-2","DOIUrl":"https://doi.org/10.1186/s12885-026-16148-2","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is often diagnosed at an advanced stage, and recurrence after initial platinum-based chemotherapy remains a major challenge. Olaparib, a poly (ADP-ribose) polymerase inhibitor, is an essential maintenance therapy, particularly for patients with homologous recombination deficiency, with proven efficacy. However, hematologic toxicity-especially anemia-is common and frequently leads to dose reductions or treatment interruptions. Japanese patients may be more susceptible to this toxicity because of smaller body size and potentially higher systemic drug exposure. Although dose reduction is recommended for patients with moderate renal impairment in Western guidelines, standardized criteria have not been established in Japan, and real-world evidence on predictors of severe anemia is limited. This study aimed to identify clinical factors associated with grade ≥ 3 anemia during olaparib therapy.</p><p><strong>Methods: </strong>We conducted a single-center retrospective cohort study of patients with ovarian cancer who initiated olaparib at Kobe City Medical Center General Hospital between July 2018 and December 2022. Patients who began therapy at external institutions were excluded. Adverse events were assessed using Common Terminology Criteria for Adverse Events version 5.0. Cox proportional hazards models were applied to evaluate predictors of grade ≥ 3 anemia, with statistical significance set at P < 0.05.</p><p><strong>Results: </strong>Among the 75 patients included the median baseline creatinine clearance (Ccr) was 75.7 mL/min. Twenty-five patients (33%) had prior exposure to pegylated liposomal doxorubicin (PLD), and eight (11%) had a baseline Ccr < 50 mL/min. Grade ≥ 3 anemia developed in 33 patients (44%). Multivariate analysis identified prior PLD exposure (hazard ratio [HR] 4.37, 95% confidence interval [CI] 2.30-8.29), baseline Ccr < 50 mL/min (HR 4.03, 95% CI 1.53-10.63), and baseline Grade 2 anemia as independent predictors. Treatment duration was significantly shorter in patients with prior PLD exposure.</p><p><strong>Conclusion: </strong>Prior PLD therapy, impaired renal function, and pre-existing anemia substantially increased the risk of severe anemia during olaparib treatment. These findings highlight the need for risk-adaptive monitoring strategies and proactive management in patients with high risk for severe anemia. Further studies with larger cohorts of patients with renal impairment are recommended to support dose-adjustment strategies and optimize treatment safety.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ITPP in early pancreatic zebrafish xenografts mildly impacts tumor cell death without interfering with vascular normalization.","authors":"Raefa Abou Khouzam, Filipa Amorim, Ayesha Rifath, Leila Thaliffdeen, Premalatha Ragupathi, Husam Nawafleh, Vanda Povoa, Miguel Cruz-Ribeiro, Jean-Marie Lehn, Rita Fior, Perparim Limani, Salem Chouaib","doi":"10.1186/s12885-026-16107-x","DOIUrl":"https://doi.org/10.1186/s12885-026-16107-x","url":null,"abstract":"<p><strong>Background: </strong>Myo-inositol trispyrophosphate (ITPP) is an anti-hypoxic small molecule that acts as an allosteric effector of hemoglobin in erythrocytes. To capture the early and dynamic effects of ITPP on tumor vasculature and cell viability, we employed a rapid zebrafish xenograft model of pancreatic ductal adenocarcinoma (PDAC) that enables real-time, single-cell-resolution imaging.</p><p><strong>Methods: </strong>Two PDAC cell lines were used to establish xenografts in wildtype and transgenic zebrafish lines. A double transgenic that permits the visualization of both vessels and erythrocytes was included to determine the impact of ITPP on vascular function. The effects of ITPP alone and in combination with multimodal chemotherapy (FOLFIRINOX) on PDAC tumor proliferation, apoptosis and size were investigated using whole-mount immunostaining and confocal microscopy.</p><p><strong>Results: </strong>Within a short treatment window, ITPP produced a detectable enhancement in the number of xenografts with erythrocyte-positive tumor-associated vessels, suggesting an early trend toward vessel functionality. This mild effect, however, came with no measurable changes in vessel architecture. While ITPP did not impact the cytotoxic potency of FOLFIRINOX, ITPP-treated xenografts displayed enhanced apoptosis in vivo. This came without any cytotoxicity in vitro, indicating that its mild pro-apoptotic activity is mediated indirectly, presumably through the tumor microenvironment (TME).</p><p><strong>Conclusions: </strong>Overall, we could not detect major effects of ITPP in the zebrafish xenograft model, possibly due to the lack of a hypoxic TME. This illustrates the model's shortcomings when investigating oxygen-modulating agents. We propose that experiments such as pre-treatment of tumor cells with hypoxic agents could overcome this, potentially expanding the utility and versatility of the zebrafish model.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and imaging characteristics of phosphaturic mesenchymal tumors: a case series analysis.","authors":"Haifeng Hou, Xiaofeng Zhou, Lijun Zhang","doi":"10.1186/s12885-026-16134-8","DOIUrl":"https://doi.org/10.1186/s12885-026-16134-8","url":null,"abstract":"<p><strong>Objective: </strong>To characterize the clinical, biochemical, pathological, and multimodal imaging features of phosphaturic mesenchymal tumors (PMTs).</p><p><strong>Methods: </strong>We retrospectively reviewed 10 patients with pathologically confirmed PMT. Clinical presentation, laboratory findings, histopathologic and immunohistochemical features, and imaging manifestations across multiple modalities were systematically analyzed.</p><p><strong>Results: </strong>All patients presented with long-standing fatigue and bone pain. Preoperative laboratory tests revealed varying degrees of hypophosphatemia and elevated alkaline phosphatase, while postoperative serum phosphate levels gradually normalized. Histopathology demonstrated heterogeneous morphologies. Immunohistochemistry showed consistent SATB2 and SSTR2 positivity in tested cases, whereas the Ki-67 proliferation index ranged from 1% to 15%. On CT, primary lesions appeared as soft-tissue density masses or ground-glass-like nodules, often with irregular calcification and focal bone destruction. MRI demonstrated hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and moderate to marked heterogeneous enhancement. Both [¹⁸F]F-OC PET/CT and [¹⁸F]F-FDG PET/CT revealed variable degrees of radiotracer uptake in all lesions.</p><p><strong>Conclusion: </strong>PMTs are characterized by typical TIO-related clinical and biochemical abnormalities, and SATB2 and SSTR2 are highly sensitive immunohistochemical markers for definitive diagnosis. Whole-body [¹⁸F]F-OC PET/CT, targeting somatostatin receptors, serves as a highly specific first-line modality for tumor localization. Dedicated CT and MRI provide essential anatomic characterization for surgical planning, while [¹⁸F]F-FDG PET/CT offers complementary, non-tumor-specific metabolic information. [^99mTc]Tc-MDP planar bone scintigraphy is useful for assessing the systemic skeletal burden of osteomalacia. This stepwise, multimodal approach improves diagnostic accuracy and supports timely surgical management.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPINK4 affected M2 macrophage polarization to promote colorectal cancer malignant phenotype by PI3K/AKT pathway.","authors":"Mingxiao Cao, Jiaqi Hao, Lixin Jiang","doi":"10.1186/s12885-026-16126-8","DOIUrl":"https://doi.org/10.1186/s12885-026-16126-8","url":null,"abstract":"<p><p>This study aimed to elucidate the oncogenic role of SPINK4 in colorectal cancer (CRC) and its underlying mechanism regulating macrophage polarization in the tumor microenvironment. In vitro, we constructed SPINK4-overexpressing and SPINK4-knockdown CRC cell lines (HT29 and HCT116) to evaluate their effects on cell proliferation, migration, and invasion. We then established a macrophage-CRC cell co-culture system to explore whether SPINK4 promotes macrophage recruitment and M2 polarization. Mechanistically, we not only regulated the PI3K/AKT pathway using inhibitor LY294002 and activator 740Y-P but also specifically knocked down PI3K via small interfering RNA (siRNA) to confirm if SPINK4's function depends on this pathway. In vivo, we established HCT116 xenograft models in nude mice, monitored tumor volume and weight, evaluated tumor proliferation by Ki67 immunohistochemistry, quantified tumor-infiltrating macrophages by flow cytometry, and detected M1/M2 macrophage marker expression by RT-qPCR. Experimental results showed SPINK4 overexpression significantly enhanced CRC cell proliferation, migration, and invasion, induced macrophage recruitment and M2 polarization, and upregulated IL-33, IL-4, IL-10, CSF1, CCL2, and VEGF-C secretion. Inhibiting PI3K/AKT reversed these effects. In vivo, SPINK4 overexpression activated PI3K/AKT, promoting tumor growth and M2 macrophage infiltration. Collectively, SPINK4 acts as an oncogene to promote macrophage recruitment and M2 polarization via PI3K/AKT, driving CRC malignant progression.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the abscopal-like effect of radioimmunotherapy on sentinel lymph nodes in H22 hepatocellular carcinoma via dynamic lymphography.","authors":"Hui Wang, Dengyun Chen, Zhehan Liu, Xuefeng Zhao, Jinzhou Zhang, Dan Zhang","doi":"10.1186/s12885-026-16140-w","DOIUrl":"https://doi.org/10.1186/s12885-026-16140-w","url":null,"abstract":"<p><strong>Background: </strong>The synergistic suppressive effects of the radioimmunotherapy-induced abscopal effect on distant non-irradiated tumors have recently emerged as a research hotspot. However, studies on its specific regulatory role in adjacent sentinel lymph nodes (SLNs) remain limited. The deep location and small size of SLNs hinder the monitoring of treatment-related changes, underscoring the need for lymphography-based approaches. In this study, we aimed to evaluate the abscopal-like effect of radioimmunotherapy on SLNs in an H22 hepatocellular carcinoma mouse model via dynamic lymphography.</p><p><strong>Methods: </strong>H22 murine hepatocarcinoma cells were transplanted into the right hind foot sole of C57BL/6 mice. Fourteen days post-inoculation, mice with SLNs were selected and divided into six groups: control, isotype control Ig, anti-PD-1 alone, irradiation (IR) alone, irradiation + isotype control Ig, and IR + anti-PD-1. The volume and weights of tumors and non-irradiated SLNs were measured. The SLNs were imaged with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) dynamic lymphography at 14, 21, and 28 days post-inoculation. CD8 immunohistochemistry assays were performed to assess CD8⁺ T cell infiltration.</p><p><strong>Results: </strong>In this mouse model, the IR + anti-PD-1 combination treatment exerted a marked suppressive effect on the growth of both irradiated tumors and non-irradiated SLNs, demonstrating a robust enhancement of the abscopal-like effect compared with the monotherapy groups. Mechanistic investigations demonstrated elevated CD8⁺ T cell infiltration in non-irradiated SLNs, suggesting that enhanced systemic anti-tumor immunity mediated the effect. Dynamic ¹⁸F-FDG PET lymphography enabled clear visualization of SLNs as early as 30 s post-injection, with sustained imaging clarity for over 30 min. This method also demonstrated decreased radioactive accumulation in irradiated tumors and non-irradiated SLNs, confirming an enhanced abscopal-like effect with the IR and anti-PD-1 combination approach.</p><p><strong>Conclusions: </strong>Our data demonstrate that the regression of SLNs adjacent to the irradiation field, mediated by the abscopal-like effect of radioimmunotherapy, can be sensitively and effectively tracked via dynamic ¹⁸F-FDG lymphography. Furthermore, our findings provide an effective and straightforward lymphographic approach with substantial translational potential for assessing the efficacy of the radioimmunotherapeutic abscopal-like effect against SLNs.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}