Oncology Research最新文献

{"title":"Research Progress on Signaling Pathways in Breast Cancer Bone Metastasis.","authors":"Yunhong Li, Tianqi Li, Fenglian Liang, Lu Kuang, Yizhi Li, Hongsheng Li","doi":"10.32604/or.2026.079898","DOIUrl":"10.32604/or.2026.079898","url":null,"abstract":"<p><p>Breast cancer (BC) has become the most commonly diagnosed malignant tumor among women worldwide, with approximately 70% of patients with advanced BC developing bone metastases. These metastases trigger bone destruction and skeletal-related events (SREs) and significantly reduce patient survival. In recent years, research into the mechanisms underlying BC bone metastasis has advanced rapidly. Molecular biological and genomic studies have revealed that BC bone metastasis is co-regulated by multiple signaling pathways through crosstalk between BC cells and the bone microenvironment. This review analyzes the research progress of signaling pathways involved in BC bone metastasis and systematically elaborates four core cascades: Wingless-related integration site (Wnt)/β-catenin, transforming growth factor-β (TGF-β), RANK/receptor activator of nuclear factor-κB ligand (RANKL)/osteoclastogenesis inhibitory factor (OPG), and phosphatidylinositol 3-Kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR). It explains how each pathway mediates epithelial-mesenchymal transition (EMT), excessive Osteoclast (OC) activation, maintenance of cancer stem cell stemness, and the formation of an immunosuppressive microenvironment. The positive feedback loops and reciprocal crosstalk between these pathways are also summarized, which together fuel the vicious cycle of osteolytic bone metastasis. This paper further consolidates therapeutic strategies targeting the aforementioned signaling pathways and outlines cutting-edge therapeutic approaches and emerging research hotspots. Nevertheless, critical obstacles including complex pathway compensation, drug resistance, and dysregulated bone immunity remain major bottlenecks hindering clinical translation. Future research will leverage single-cell sequencing and multi-omics technologies to identify pivotal molecular targets and develop potent combinatorial therapies. Such advances will facilitate the implementation of precise, individualized treatment for BC bone metastasis and ultimately improve the quality of life and long-term clinical outcomes of patients with advanced bone-metastatic disease.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"14"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal Doxorubicin Induces PD-L1-High Tumor-Associated Macrophages and Sensitizes Triple-Negative Breast Cancer to PD-L1 Blockade.","authors":"Yu Zheng, Peng Zheng, Yidan Zheng, Zihan Xi, Tao Huang","doi":"10.32604/or.2026.087138","DOIUrl":"10.32604/or.2026.087138","url":null,"abstract":"<p><p><b>Objective:</b> Liposomal doxorubicin (L-DOX) may alter macrophage-mediated immune regulation in triple-negative breast cancer (TNBC), but its role in programmed death-ligand 1 (PD-L1)-associated immune escape remains unclear. This study aimed to determine whether L-DOX induces a macrophage-centered PD-L1 response and affects the efficacy of PD-L1 blockade in TNBC. <b>Methods:</b> Public bulk and single-cell transcriptomic datasets, bone marrow-derived macrophage models, CD8⁺ T-cell co-culture assays, promoter-binding analyses, and syngeneic EO771 and 4T1 TNBC mouse models were used to examine PD-L1 regulation and immune function after L-DOX treatment. <b>Results:</b> The principal findings were that L-DOX preferentially induced a PD-L1-high macrophage state and sensitized TNBC tumors to PD-L1 blockade. DOX-containing therapy was associated with PD-L1 upregulation enriched in tumor-associated macrophages, and L-DOX induced stronger macrophage PD-L1 expression than free DOX or taxane-based agents. Mechanistically, L-DOX accumulation triggered DNA damage-associated ATM-p53 and cGAS-STING signaling, leading to RELA/p65-dependent NF-κB activation and PD-L1 transcription. Functionally, L-DOX-conditioned macrophages suppressed CD8⁺ T-cell activation, proliferation, and tumor-cell killing, whereas PD-L1 blockade restored CD8⁺ effector function, promoted pro-inflammatory macrophage features, and improved tumor control in EO771 and 4T1 models compared with either monotherapy. <b>Conclusion:</b> L-DOX induces a PD-L1-high macrophage state with immunosuppressive features that constrains antitumor T-cell responses. Combining L-DOX with PD-L1 blockade may provide a rational chemoimmunotherapy strategy for TNBC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"28"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: T-box Transcription Factor Tbx3 Contributes to Human Hepatocellular Carcinoma Cell Migration and Invasion by Repressing E-Cadherin Expression.","authors":"","doi":"10.32604/or.2026.092122","DOIUrl":"https://doi.org/10.32604/or.2026.092122","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504017X15145624664031.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"31"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNX9 Orchestrates Lung Metastasis via EGFR-ERK Signaling and Actin Cytoskeleton Remodeling in Breast Cancer.","authors":"Qingqing Liu, Lei Li, Kumar Ganesan, Yang Jiang, Kewu Zeng, Yue Sui, Xinyuan Guan, Rongfang He, Jianping Chen","doi":"10.32604/or.2026.082536","DOIUrl":"10.32604/or.2026.082536","url":null,"abstract":"<p><p><b>Objectives:</b> Sorting nexin 9 (SNX9) participates in endocytic trafficking and has been connected to several malignancies, but its involvement in breast cancer (BC) remains incompletely resolved. This work was designed to examine whether SNX9 supports BC progression and investigate signaling and cytoskeletal processes associated with its activity. <b>Methods:</b> The clinical relevance of SNX9 was assessed using bioinformatics analysis of publicly available cancer databases. Lentiviral vectors were used to establish BC cell models with stable SNX9 overexpression or knockdown. Both cellular (proliferation and motility) and murine (tumor growth and metastatic colonization) experiments were implemented to functionally characterize the SNX9-mediated phenotypes. The underlying mechanisms were investigated via western blotting, immunofluorescence, co-immunoprecipitation, and pathway-focused analyses. <b>Results:</b> Across the analyzed datasets, greater SNX9 abundance was linked to worse overall survival outcomes in BC patients. Functionally, SNX9 upregulation conferred increased proliferative, migratory, and invasive capacities <i>in</i> <i>vitro</i> and contributed to both primary tumor enlargement and distant metastatic spread <i>in</i> <i>vivo</i>, whereas SNX9 depletion produced the reciprocal phenotypes. SNX9 silencing also increased the G2/M cell fraction and disrupted actin cytoskeletal organization mechanistically linked to reduced Ras-related C3 botulinum toxin substrate 1 (Rac1)/cell division cycle 42 homolog (Cdc42) activation and the subsequent impairment of lamellipodial and filopodial protrusion. Additionally, co-immunoprecipitation substantiated the physical coupling between SNX9 and the scaffold protein tyrosine kinase substrate with five SH3 domains (TKS5), which correlated with the invasive behavior of BC cells. <b>Conclusion:</b> Collectively, our findings establish SNX9 as a critical oncoprotein that drives BC progression by coordinating proliferative epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling and cytoskeletal dynamics through interactions with TKS5 and Rac1/Cdc42. Clinically, SNX9 qualifies as a promising prognostic classifier and a rational target for therapeutic intervention.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"22"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: miR-126 Functions as a Tumor Suppressor by Targeting SRPK1 in Human Gastric Cancer.","authors":"","doi":"10.32604/or.2026.092118","DOIUrl":"https://doi.org/10.32604/or.2026.092118","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504018X15180508535835.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"29"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FSCN1 Modulates Fatty Acid Metabolism and the Coordinated Activation of AKT/mTOR and p38 MAPK Pathways in Colorectal Cancer Cells.","authors":"Zhen Li, Xinya Yu, Boning Wu, Jialin Zhang, Xinyu Ju, Yajun Wang, Jieli Song, Qiao Liu, Peng Huang, Qi Ding, Yupeng Wu","doi":"10.32604/or.2026.084987","DOIUrl":"10.32604/or.2026.084987","url":null,"abstract":"<p><p><b>Background:</b> Fascin actin-bundling protein 1 (<i>FSCN1</i>) modulates the expression of key lipogenic enzymes fatty acid synthase (<i>FASN</i>) and stearoyl-CoA desaturase (<i>SCD1</i>) in colorectal cancer (CRC), but the underlying mechanisms remain elusive. <b>Methods:</b> Bioinformatics analyses were performed to evaluate FSCN1 expression and its prognostic value in CRC. Intracellular lipid levels following <i>FSCN1</i> knockdown were assessed by Nile Red/DAPI co-staining and triglyceride quantification, and further validated by Oil Red O staining of xenograft tumors. Expression levels of key metabolic enzymes were measured by qRT-PCR and Western blotting. RNA sequencing identified FSCN1-associated pathways, which were functionally investigated using pharmacological inhibitors. <b>Results:</b> FSCN1 was significantly upregulated in CRC (<i>p</i> < 0.001; AUC = 0.796) and was correlated with poorer overall survival (<i>p</i> = 0.018). FSCN1 depletion reduced intracellular lipid accumulation, accompanied by downregulation of lipogenic mediators-sterol regulatory element-binding transcription factor 1 (<i>SREBF1</i>; protein product: SREBP1), FASN, and SCD1-and upregulation of peroxisomal fatty acid oxidation (FAO)-related factors-peroxisome proliferator-activated receptor alpha (<i>PPARA</i>; protein product: PPARα) and acyl-CoA oxidase 1 (<i>ACOX1</i>). Mechanistically, FSCN1 was associated with activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) and p38 mitogen-activated protein kinase (p38 MAPK) pathways; pharmacological inhibition with LY294002 or SB203580 phenocopied the lipid-lowering effects of <i>FSCN1</i> knockdown. <b>Conclusion:</b> Collectively, these findings link FSCN1 to the AKT/mTOR/SREBP1/(FASN/SCD1) lipogenic axis and the p38 MAPK/PPARα/ACOX1 peroxisomal FAO pathway, implicating FSCN1 in lipid metabolic regulation and CRC progression, while suggesting a putative functional regulatory axis and a promising candidate therapeutic target for CRC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"24"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Neoadjuvant Chemotherapy, Chemoimmunotherapy, and Upfront Radical Cystectomy in High-Risk Bladder Cancer: A Single-Center Retrospective Study.","authors":"Shaohua Chen, Xiao Gan, Ping Lv, Qinggui Meng, Xiaocao Lin, Qingyun Zhang","doi":"10.32604/or.2026.083704","DOIUrl":"10.32604/or.2026.083704","url":null,"abstract":"<p><p><b>Background:</b> While radical cystectomy is standard for muscle-invasive bladder cancer (MIBC), micrometastasis-related recurrence is common. Cisplatin-based neoadjuvant therapy (NAT) confers modest benefits, while immune checkpoint inhibitors (ICIs) provide new efficacy-enhancing strategies. This study aims to compare the efficacy and safety of ICIs with chemotherapy (NAC-ICI), neoadjuvant chemotherapy (NAC), and no neoadjuvant therapy (NNAT). It also explores potential biomarkers predictive of NAT response and evaluates the real-world efficacy of NAC-IC. <b>Method:</b> This single-center retrospective analysis included 80 radical cystectomy patients, with 51 NNAT group and 29 in the NAT group. Survival outcomes were evaluated by Kaplan-Meier survival curves, with log-rank test and restricted mean survival time (RMST) for comparisons. Pathological responses were assessed by complete response (pCR) and downstaging (pDS). Treatment-related adverse events (TRAEs) and predictive hematological biomarkers were analyzed. <b>Results:</b> Kaplan-Meier curves showed NAT is non-significant survival advantage over NNAT (<i>p</i> = 0.30). The RMST analysis showed the NAC-ICI had significantly longer RMST than the NNAT (56.00 vs. 47.73 months; Δ = +8.27 months; <i>p</i> = 0.0008). Fisher's exact test showed that NAC-ICI had a numerically higher pCR rate (42.10%) than NAC (20.00%), but the difference was non-significant (<i>p</i> = 0.414) ROC analysis showed baseline platelet count (PLT) was a significant negative predictor of pCR after NAC-ICI. <b>Conclusions:</b> This study indicates potential feasibility and safety of NAT for MIBC patients. Chemoimmunotherapy trends toward better pathological and survival outcomes than chemotherapy alone, but no statistically significant differences were observed. Baseline PLT may be a potential prdictive biomarker.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"16"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OTUD7B Activates the Caspase-8-RIPK1-NEMO Complex-Regulated NF-κB Pathway to Promote Triple-Negative Breast Cancer Metastasis.","authors":"Fiona Tsui-Fen Cheng, Kung-Ju Chen, Jing-Quan Zheng, Hui-Wen Chiu, Hui-Yu Lin, Yuan-Feng Lin","doi":"10.32604/or.2026.081093","DOIUrl":"10.32604/or.2026.081093","url":null,"abstract":"<p><p><b>Background:</b> Metastatic dissemination of triple-negative breast cancer (TNBC) to distant organs, such as the lungs and brain, poses a significant threat to patient survival. Nevertheless, the molecular basis driving TNBC metastasis remains largely elusive. In the present study, we elucidated the role and underlying mechanism of OTU deubiquitinase 7B (OTUD7B) in promoting TNBC metastasis. <b>Methods:</b> The Cancer Genome Atlas (TCGA)/K-M Plotter databases were used for determining the prognostic significance of OTUD7B in TNBC patients. Cell migration and lung colony-forming assays were performed to evaluate the metastatic potential of TNBC cells. A cycloheximide-chase assay was employed to examine the effect of OTUD7B on Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) Essential Modulator (NEMO) protein degradation in TNBC cells. Flow-cytometric analyses were performed to examine OTUD7B effects on TNBC necroptosis. <b>Results:</b> OTUD7B is significantly (<i>p</i> < 0.001) upregulated in TNBC and correlates with poor distant metastasis-free survival (log-rank <i>p</i> < 0.001, <i>n</i> = 424). Its knockdown suppresses, whereas overexpression enhances, the metastatic potential of TNBC cells <i>in vitro</i> and <i>in vivo</i>, dependent on its deubiquitinating activity. Mechanistically, OTUD7B regulates the ubiquitination of Caspase-8 and NEMO, thereby modulating NF-κB signaling through the Caspase-8-RIPK1-NEMO axis. OTUD7B depletion increases Caspase-8 activity by approximately three-fold, promotes NEMO degradation, suppresses NF-κB activation, and induces necroptosis. Conversely, OTUD7B overexpression exerts opposite effects. Pharmacological inhibition of NEMO or NF-κB attenuates OTUD7B-driven cell migration by 40-90%. <b>Conclusions:</b> The deubiquitinating activity of OTUD7B promotes TNBC metastasis by stabilizing the Caspase-8-RIPK1-NEMO axis, thereby activating the NF-κB signaling pathway. These results further suggest that targeting OTUD7B activity may be a promising therapeutic strategy for metastatic TNBC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"15"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance Mechanisms in Immunotherapy-Radiotherapy/Chemotherapy Combinations in Locally Advanced Head & Neck Squamous Cell Carcinoma.","authors":"Abbas Hussain, Daniel Thomas Jones, Rishi Kumar Nanda, Ramaditya Srinivasmurthy, Jason Ta, Yin Mon Myat, Riccesha Hattin, Jo-Lawrence Bigcas, Sisi Tian, Suparna Shah, Robert Wang, Kyaw Zin Thein","doi":"10.32604/or.2026.077918","DOIUrl":"10.32604/or.2026.077918","url":null,"abstract":"<p><p>Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) remains difficult to treat despite multimodal therapy. Immune checkpoint inhibitors (ICIs) have expanded treatment options, but phase III trials combining ICIs with chemoradiotherapy have demonstrated limited survival benefit due to complex resistance mechanisms. These include immunosuppressive tumor microenvironments, impaired DNA damage responses, hypoxia-driven adaptations, metabolic reprogramming, and oncogenic signaling via the HER receptor family. This review outlines key resistance pathways and emerging strategies to overcome them. Nanotechnology-based approaches may enhance drug delivery and modulate the tumor microenvironment, while dual inhibition of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 3 (HER3), and downstream pathways shows promise in addressing compensatory signaling. Advances in biomarkers, including programmed death-ligand 1 (PD-L1), circulating tumor DNA, metabolic profiling, and radiomics, enable improved patient selection and monitoring. Novel immune checkpoints and adoptive cellular therapies, alongside personalized and adaptive trial designs, offer potential to improve outcomes in LA-HNSCC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"5"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Insights into the Role of Peripheral Blood Immune Cell Phenotypes in Resistance to Cancer Therapies.","authors":"Allinson Olaechea, Cristina Camacho Rubio, Sara Gómez-Melero","doi":"10.32604/or.2026.079865","DOIUrl":"10.32604/or.2026.079865","url":null,"abstract":"<p><p>Peripheral blood mononuclear cell (PBMC) immunophenotyping has emerged as a promising non-invasive approach to characterize systemic immune alterations in cancer and to identify biomarkers associated with treatment response and resistance. However, current evidence remains fragmented and predominantly descriptive, with substantial heterogeneity in study design, immunophenotyping methodologies, and patient populations, limiting the identification of robust and clinically translatable immune signatures. In this review, we aim to comprehensively analyze PBMC immune phenotypes across multiple cancer types, with particular emphasis on their association with disease progression, therapeutic outcomes, and the key methodological and translational challenges that currently limit their clinical implementation. Across malignancies, conserved immune features are consistently observed, including T cell exhaustion, regulatory T cell (Treg) expansion, and upregulation of immune checkpoint molecules, reflecting chronic immune activation and dysfunction. In parallel, tumor-specific phenotype, such as peripheral helper T (Tph) cell expansion in non-small cell lung cancer, Vδ1⁺CD69⁺ γδ T cells in hepatocellular carcinoma, and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) positive dysfunctional T cells in oral squamous cell carcinoma, highlight the influence of tumor-specific immune contexts. Importantly, this review moves beyond descriptive reporting by integrating mechanistic insights into how PBMC phenotypes contribute to therapeutic resistance. Key mechanisms include immunosuppressive cytokine signaling (e.g., interleukin-10 (IL-10), transforming growth factor-β (TGF-β)), chronic antigen stimulation driving T cell dysfunction, and systemic immune-tumor crosstalk mediated by chemokine axes such as stromal cell-derived factor 1 (SDF-1)/C-X-C motif chemokine receptor 4 (CXCR4). In addition to lymphoid populations, we emphasize the contribution of myeloid cell subsets, including monocytes and myeloid-derived suppressor cells, as central regulators of immune evasion and treatment failure. Despite these advances, significant challenges remain, including the lack of standardized protocols, limited longitudinal and multicenter validation studies, and insufficient integration of multi-omics approaches. Addressing these limitations will be essential for clinical translation. Overall, this review provides a refined conceptual framework that distinguishes conserved and tumor-specific immune signatures and highlights their mechanistic relevance in therapeutic resistance, supporting the development of PBMC immunophenotyping as a tool for personalized cancer immunotherapy.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"6"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}