Medical Oncology最新文献

{"title":"Correction: LncRNA TMPO-AS1 aggravates the cisplatin resistance in cervical cancer via miR-140-5p/DNMT1 axis-mediated DNA methylation of KLK10.","authors":"Jian Yang, Zhouhong Shi, Ting Song, Yurui Shao, Shunyu Hou, Chen Cheng, Baoquan Liang, Xiaojun Yang","doi":"10.1007/s12032-026-03401-8","DOIUrl":"10.1007/s12032-026-03401-8","url":null,"abstract":"","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrodin enhances the spleen immune function in erythroleukemia by regulating T-cell receptor signaling pathway.","authors":"Sha Cheng, Yingjiang Xu, Jianping Wang, Jia Yu, Liangliang Hu, Jiming Liu, Heng Luo","doi":"10.1007/s12032-026-03388-2","DOIUrl":"10.1007/s12032-026-03388-2","url":null,"abstract":"<p><p>Erythroleukemia is a malignant hematological disorder often accompanied by severe immunosuppression, with T cell dysfunction playing a central role. Gastrodin, which is derived from Gastrodia elata, has been proven to possess various pharmacological activities such as neuroprotection and immunomodulation. However, whether it can effectively improve the immune function in erythroleukemia has not been reported. Our results demonstrated that gastrodin treatment significantly alleviated splenomegaly and inhibited the malignant progression in erythroleukemia mice. Moreover, it markedly enhanced the proliferative capacity of splenic T cells and promoted the secretion of immune - related cytokines. Mechanistically, gastrodin upregulated the expression of key molecules in the T cell receptor signaling pathway, including LCK, ZAP-70, ITK, PKC, IKK, and NFκB, at both the mRNA and protein phosphorylation levels. Notably, through integrated bioinformatics analysis, molecular docking, and cellular thermal shift assays, we found that gastrodin exhibits moderate interaction with the transcription factor Fli-1 in erythroleukemia. Collectively, this study provides the first evidence that gastrodin enhances splenic immune function in erythroleukemia by modulating the T cell receptor (TCR) signaling pathway. Cellular thermal shift assay identified Fli-1 as a protein capable of physically interacting with gastrodin, although its functional contribution remains to be further explored. These findings highlight gastrodin as a promising immunotherapeutic candidate for erythroleukemia.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotheranostics armed with folate: an integrated approach for precision targeting of glioblastoma.","authors":"Dipak B Bari, Chandrakantsing V Pardeshi","doi":"10.1007/s12032-026-03363-x","DOIUrl":"10.1007/s12032-026-03363-x","url":null,"abstract":"<p><p>Glioblastoma (GBM) is extremely difficult to treat due to the poor blood-brain barrier (BBB) penetration, strong extracellular matrix, high interstitial pressure, and restricted cellular absorption, all of which prevent efficient drug delivery. Folate-conjugated nanotheranostics have emerged as a viable way to overcome these hurdles, taking advantage of GBM cells' upregulation of folate receptors (FRs). Folate-conjugation chemistry, either by direct ligand coupling or linker-assisted surface modification, have resulted in more selective receptor-based targeting, increased stability, and regulated chemotherapeutic release inside the tumor microenvironment. These nanosystems show increased penetration and selective absorption via FR-mediated endocytosis, which allows for deeper intratumoral distribution and more effective administration of chemotherapeutics and imaging agents. Recent advances in nanomedicine-based drug delivery systems with folate-functionalization shows promise for integrated GBM diagnosis and treatment. Latest findings also suggest good biocompatibility and low systemic toxicity of folate-armed nanotheranostics; however long-term safety is still a crucial issue and need to be discussed. This review summarizes the key challenges to GBM therapy and explores how folate-decorated nanotheranostics, via tailored chemistry and increased tumoral contact, constitute a potential option for GBM precision therapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VISTA as a myeloid-centered checkpoint axis in cancer: biology, tumor microenvironment, and therapeutic implications.","authors":"Sarenur Tekiner, Rumeysa Berra Karataş, Yaren Alras, Kaan Zıkşahna, Selim Merdan, Murat Ihlamur","doi":"10.1007/s12032-026-03416-1","DOIUrl":"10.1007/s12032-026-03416-1","url":null,"abstract":"<p><p>VISTA (V-domain Ig suppressor of T-cell activation; gene symbol VSIR) has emerged as a distinct immune checkpoint with increasing relevance in cancer biology and immunotherapy. Unlike classical checkpoint pathways that are predominantly interpreted through T cell-centered suppression, accumulating evidence indicates that VISTA exerts broader and highly context-dependent immunoregulatory functions, frequently centered on myeloid cells within the tumor microenvironment. In many malignancies, VISTA is preferentially enriched in tumor-associated macrophages, myeloid-derived suppressor cells, and dendritic cells rather than being uniformly expressed by tumor cells. This compartment-specific distribution has been linked to suppressive myeloid differentiation, impaired antigen presentation, altered inflammatory cytokine programs, T-cell dysfunction, and immune exclusion. Recent studies further suggest that VISTA biology is shaped by ligand context, tissue compartment, tumor acidity, and therapy-induced adaptation, supporting its role in resistance to conventional immune checkpoint blockade in selected settings. In this review, we summarize the structural and functional features of VISTA, its expression patterns in physiological and tumor contexts, its mechanistic role in shaping the tumor microenvironment, and the current landscape of VISTA-targeted therapeutic strategies. Key unresolved questions include which VISTA binding partners dominate in vivo, how cellular source and spatial localization determine biological and prognostic meaning, and whether early pharmacodynamic target engagement will translate into durable clinical benefit. Collectively, current evidence supports the view that VISTA should be considered not simply as another inhibitory receptor, but as a dynamically regulated, myeloid-centered checkpoint axis with translational relevance in checkpoint-refractory and immune-excluded tumors. A compartment-resolved understanding of VISTA expression and function may improve prognostic interpretation, biomarker development, and patient selection for VISTA-directed therapies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential STING and p53 expression in epidermodysplasia verruciformis-associated versus non-EV cutaneous squamous cell carcinomas.","authors":"Luis Alberto Ribeiro Fróes, Walmar Roncalli Pereira de Oliveira, Paulo Stahlschmidt, Lana Luiza da Cruz Silva, Naiura Vieira Pereira, Mirian Nacagami Sotto","doi":"10.1007/s12032-026-03417-0","DOIUrl":"10.1007/s12032-026-03417-0","url":null,"abstract":"<p><p>Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by persistent cutaneous β-human papillomavirus infection and increased risk of cutaneous squamous cell carcinoma (cSCC). The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway links cytosolic DNA sensing, genomic instability and innate immune activation, but its expression in EV-associated cSCC remains poorly defined. We quantified STING, p53 and BCL2 immunohistochemical expression in tissue microarrays containing 47 EV-associated and 83 non-EV cSCCs. Tumor H-scores were medians across valid cores; primary comparisons used patient-clustered generalized estimating equations (GEE). STING expression was higher in EV-associated tumors (median H-score 192.4 vs. 149.5); in grade-adjusted GEE, EV status was associated with a + 37.2-unit difference (95% confidence interval [CI] 23.4-51.0; p < 0.001). The EV-non-EV STING difference varied by histological grade (interaction p = 0.0067), with the largest estimated difference in grade 1 tumors. p53 expression was also higher in EV tumors (97.7 vs. 36.3; adjusted difference + 43.8, 95% CI 18.8-68.8; p < 0.001), and EV tumors had higher odds of belonging to a higher p53 tertile (odds ratio [OR] 3.54, 95% CI 1.98-6.32; p < 0.001). BCL2 remained low and was not significantly associated with EV (adjusted difference - 1.93, 95% CI - 4.84 to 0.98; p = 0.193). STING and p53 remained positively associated after adjustment for histological grade, EV status and patient clustering. These findings define an altered STING protein-expression phenotype in EV-associated cSCC, accompanied by increased p53 expression but no independent BCL2 association, and support functional investigation of cGAS-STING signaling.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977175","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":"Intratumoral PD-1⁺LAG-3⁺CD8⁺ T cells are associated with improved prognosis in gastric cancer.","authors":"Dan Liu, Zirui Xue, Kuan Yu, Zhaodong Sun, Guoxing Ma, Junjie Zhao, Haojie Li, Yihong Sun, Zhaoming Wang, Xuefei Wang","doi":"10.1007/s12032-026-03384-6","DOIUrl":"10.1007/s12032-026-03384-6","url":null,"abstract":"<p><strong>Purpose: </strong>PD-1 and LAG-3 are frequently used as markers of T cell exhaustion, yet the prognostic relevance and phenotypic characteristics of PD-1⁺LAG-3⁺CD8⁺ T cells in gastric cancer (GC) remain poorly defined. This study aimed to investigate their association with clinical outcomes and characterize their immune characteristics across independent GC cohorts.</p><p><strong>Methods: </strong>Four independent GC cohorts were analyzed: the Zhongshan Hospital cohort (ZSGC, n = 298), The Cancer Genome Atlas cohort (TCGA, n = 371), an Immune Checkpoint Blockade cohort (ICB, n = 45), and the Yonsei cohort (n = 433). Intratumoral PD-1⁺LAG-3⁺CD8⁺ T cell infiltration was quantified by immunofluorescence staining and transcriptomic gene signature scoring. Survival analysis was performed using Kaplan-Meier estimation and multivariate Cox regression. Functional characterization was performed by flow cytometry on resected GC tissue. The immune microenvironment composition was evaluated using computational analyses.</p><p><strong>Results: </strong>PD-1⁺LAG-3⁺CD8⁺ T cells were enriched within tumors compared to adjacent normal mucosa, and their infiltration correlated with advanced tumor stage, poor differentiation, microsatellite instability, and Epstein-Barr virus (EBV)-positive molecular subtypes. High intratumoral infiltration was significantly associated with improved overall survival in both the ZSGC and TCGA cohorts, whereas single-positive PD-1⁺CD8⁺ or LAG-3⁺CD8⁺ T cells showed no such association. In the ICB cohort, higher infiltration was associated with a higher response rate to pembrolizumab. Intratumoral PD-1⁺LAG-3⁺CD8⁺ T cells exhibit an activated phenotype characterized by increased expression of CD137, IFN-γ, perforin, and CXCL13, along with elevated TCF7 and lower PD-1 levels, suggesting a tumor-reactive, pre-exhausted state. High infiltration was further associated with an immune-active tumor microenvironment.</p><p><strong>Conclusions: </strong>High intratumoral infiltration of PD-1⁺LAG-3⁺CD8⁺ T cells is associated with favorable prognosis and an immune-active microenvironment in GC. These cells display phenotypic features consistent with a pre-exhausted state and may serve as independent prognostic biomarkers and candidate predictive biomarkers for immunotherapy stratification.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fgl-1 promotes the progression of endometrial adenocarcinoma through PI3K/AKT signal pathway.","authors":"Wenjing Sun, Weijia Kong, Xinyu Yu, Kaiyue Shang, Qianqian Li, Hui Zhang","doi":"10.1007/s12032-026-03375-7","DOIUrl":"10.1007/s12032-026-03375-7","url":null,"abstract":"<p><p>Endometrial adenocarcinoma (EAC) represents a prevalent malignancy of the female reproductive tract. Fibrinogen-like protein 1 (Fgl-1), an emerging immune checkpoint ligand expressed by tumor cells, mediates immunosuppression by binding to lymphocyte activation gene 3 (Lag-3). However, the clinicopathological significance and oncogenic role of Fgl-1 in EAC remain poorly understood. This study aimed to assess the role of Fgl-1 expression in EAC using immunohistochemistry. The effects of Fgl-1 on viability, migration, and invasion were assessed using the CCK-8 test, cell clone generation, wound healing, and cell migration and invasion assays. A Western blot was used to determine how Fgl-1 affects the outcome of epithelial-mesenchymal transition (EMT)-associated proteins and to investigate the expression of proteins involved in related signaling pathways. Fgl-1 was markedly overexpressed in EAC tissues compared with normal endometrium (P<0.01), with expression positively correlated to tumor grade (P=0.011). Western blotting confirmed high Fgl-1 levels in EAC cell lines, particularly HEC1B and KLE, which were used for knockdown experiments. Lentiviral silencing reduced Fgl-1 expression by 60%, leading to decreased cell viability, proliferation, migration, and invasion. Furthermore, Fgl-1 suppression inhibited PI3K/AKT signaling in KLE cells, suggesting its oncogenic role via EMT regulation and pathway activation. Together, these findings demonstrate that Fgl-1 acts as an oncogenic driver in EAC by activating PI3K/AKT signaling to promote tumor progression and EMT, suggesting that targeting the Fgl-1 pathway represents a promising therapeutic strategy for EAC immunotherapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HGF/c-MET signaling induces glutamine metabolism in MET-amplified head and neck squamous cell carcinoma via MAPK/ERK-dependent induction of GLS-1.","authors":"Marius Hörner, Florian Mersdorf, Natalie Burkard, Andreas Vollmer, Babak Saravi, Tobias Renner, Julian Volland, Alexander Kübler, Nicolas Schlegel, Stefan Hartmann","doi":"10.1007/s12032-026-03409-0","DOIUrl":"10.1007/s12032-026-03409-0","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is a common malignancy characterized by poor survival due to recurrence, metastasis and therapy resistance. In addition to genetic alterations, metabolic reprogramming is a hallmark of HNSCC and contributes to tumor progression and treatment failure. The hepatocyte growth factor (HGF)/c-MET signaling pathway is frequently activated in head and neck squamous cell carcinoma (HNSCC), where it promotes tumor cell proliferation, invasion, and increased glucose metabolism. However, its contribution to the regulation of glutamine metabolism in HNSCC remains largely unexplored. Basal GLS-1 expression was compared between primary human oral keratinocytes (HOK) and HNSCC cell lines with distinct MET status (Detroit 562, FaDu, and SCC-154). Subsequently, HNSCC cell lines were stimulated with HGF, and GLS-1 expression was assessed by quantitative PCR and Western blotting. Functional effects were evaluated using wound-healing assays, enzymatic quantification of extracellular glutamine and glutamate, and Seahorse-based mitochondrial respiration analysis. GLS-1 was silenced using siRNA to determine its functional relevance. In addition, transcriptomic data from the TCGA-HNSC cohort were analyzed to evaluate the clinical association between MET signaling, MAPK/ERK pathway activity, and GLS1 expression. HGF stimulation selectively induced GLS-1 expression in MET-amplified Detroit 562 cells at both mRNA and protein levels, whereas MET wild-type cells remained largely unaffected. Mechanistically, HGF triggered robust ERK1/2 activation, and pharmacological inhibition of c-MET or ERK signaling abrogated GLS-1 induction. Functionally, HGF increased glutamine consumption, glutamate production, and mitochondrial respiratory capacity in a GLS-1-dependent manner, while GLS-1 silencing significantly impaired HGF-induced cell migration and mitochondrial respiration. Importantly, analysis of TCGA-HNSC tumors revealed significant correlations between MET expression, MAPK/ERK pathway activity, and GLS1 expression, supporting the clinical relevance of the identified signaling axis. Together, these findings identify GLS-1 as a downstream effector of HGF/c-MET-MAPK/ERK signaling in MET-amplified HNSCC and link oncogenic signaling to glutamine metabolism and mitochondrial function. The observed associations in TCGA patient tumors further support the clinical relevance of this pathway and suggest that targeting glutaminase or ERK signaling may represent a promising therapeutic strategy in c-MET-driven HNSCC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977234","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":"Folate-modified chitosan nanocarriers in precision oncology: molecular engineering, targeted drug delivery, and clinical perspectives.","authors":"Mohammad Sameer Khan, Waleed Hassan Almalki","doi":"10.1007/s12032-026-03415-2","DOIUrl":"10.1007/s12032-026-03415-2","url":null,"abstract":"<p><p>Cancer remains a major cause of morbidity and mortality worldwide, and the effectiveness of conventional chemotherapy is frequently limited by poor tumor selectivity, systemic toxicity, rapid drug clearance, and multidrug resistance. These limitations have accelerated the development of targeted nanocarrier systems, with folate-functionalized chitosan nanoparticles (NPs) emerging as promising platforms for precision cancer therapy. Chitosan possesses favorable biocompatibility, biodegradability, mucoadhesive properties, and chemical versatility, while folate conjugation enables active targeting through folate receptor (FR)-mediated endocytosis. As FRs are overexpressed in several malignancies, including breast, ovarian, lung, colorectal, pancreatic, and cervical cancers, folate-functionalized NPs have the potential to enhance selective drug delivery, improve tumor accumulation, and minimize off-target toxicity. Recent advancements in smart and multifunctional nanocarriers, including MXene quantum dot polymer nanocomposites, have further emphasized the importance of surface engineering, multifunctionality, controlled drug release, and safety evaluation in the development of next-generation targeted drug delivery systems. Folate-functionalized chitosan NPs represent a biologically relevant and versatile class of targeted nanocarriers, offering the potential to enhance cellular uptake, provide sustained and controlled drug release, improve anticancer efficacy, and reduce systemic toxicity compared with non-targeted formulations. Important translational challenges, including reproducibility, formulation stability, interpatient variability in FR expression, immunogenicity, scalability, and regulatory considerations, also require careful attention for successful clinical development. Overall, this review provides a comprehensive overview of the design, synthesis, functionalization, therapeutic applications, pharmacokinetics, biodistribution, safety profiles, and clinical translation potential of folate-functionalized chitosan NPs for precision cancer therapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the barrier: Engineering the tumor-immune-soil nexus-a mechanistic blueprint for integrating Traditional Chinese Medicine with immunotherapy in metastatic colorectal cancer.","authors":"Yu Sun, Yandong Li, Haopeng Jiang, Xueyan Liu, Shuai Yu, Yuqi Liu","doi":"10.1007/s12032-026-03397-1","DOIUrl":"10.1007/s12032-026-03397-1","url":null,"abstract":"<p><p>Metastatic colorectal cancer (mCRC) presents a stark immuno-oncologic dichotomy: while microsatellite instability-high (MSI-H) tumors respond to immune checkpoint inhibitors (ICIs), the vast majority of microsatellite-stable (MSS) cases remain refractory, underscoring a critical need for novel strategies to convert \"cold\" tumors into \"hot\" ones. This review advances the hypothesis that Traditional Chinese Medicine (TCM) can serve as a formula-defined ecological conditioner within the tumor-immune-soil nexus. We propose a mechanistic blueprint where TCM formulas, rather than acting as nonspecific immunostimulants, function as multi-target systems that re-engineer the tumor microenvironment. The framework integrates three actionable pillars: (1) remodeling the gut microbiome to restore immune-competent consortia and metabolic flux, (2) reprogramming the myeloid compartment away from suppressive M2 macrophages and MDSCs toward immunostimulatory states, and (3) inducing immunogenic cell death to generate critical danger signals. By translating classical concepts like the Gan Pi axis into modern immunometabolism, we propose that TCM can prime the \"soil\" to sensitize MSS mCRC to ICI therapy. However, realizing this potential requires a paradigm shift from descriptive reports to rigorous, biomarker-driven trials. A crucial point is that the nature of a significant portion of existing human evidence remains observational, cross-sectional, or case-control; this limits causal inference and hinders the reconstruction of the long-term temporal sequence extending from the reciprocal dynamics of the immune system and microbiome to cancer progression or treatment response. We conclude that the future of TCM-ICI integration lies in standardized, chemically characterized formulas evaluated within adaptive platform trials, utilizing spatial transcriptomics and microbiome-humanized models to validate true cold-to-hot conversion.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}