Search Results (694)

Background/Objectives: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before 50 years of age, is increasing worldwide and may exhibit molecular features distinct from late-onset colorectal cancer (LOCRC). This study aimed to identify EOCRC-associated genes and evaluate the functional relevance of the leading candidate. Methods: Public transcriptomic datasets were used for age-stratified candidate-gene discovery and validation. Overall survival analysis prioritized candidates, followed by loss-of-function studies and pathway-focused analyses in colorectal cancer cell lines. Results: CEMIP, NKD2, and FOXQ1 were elevated in the EOCRC groups in the discovery and integrated validation analyses. Among them, only CEMIP was significantly associated with poorer overall survival. HCT116 and HT29 cells showed relatively high endogenous CEMIP expression, and CEMIP knockdown reduced relative viable cell biomass and migration in wound-healing and Transwell assays. CEMIP-associated transcripts were enriched in several pathways, including Hedgehog, Wnt/β-catenin, and TGF-β signaling. In TCGA colon adenocarcinoma samples, CEMIP correlated most strongly with PTCH1; however, the correlations with other Hedgehog components were weak or absent. CEMIP silencing decreased PTCH1 and GLI1 transcripts while increasing SMO, suggesting a coordinated but non-linear relationship. Conclusions: CEMIP is an EOCRC-associated candidate biomarker and a functional contributor to colorectal cancer cell viability and migration. Its relationship with PTCH1-related Hedgehog signaling is exploratory and warrants direct mechanistic validation. Full article

The underexplored Passerini–Smiles reaction (PSR), a variant of the 3-component Passerini reaction (3CPR), was successfully employed to create a tailored library of phenoxy-indoline carboxamide derivatives based on a fragment-based hybrid drug design strategy. Under mild conditions, inexpensive and commercially available isatin was utilized as a privileged carbonyl core, combined with electron-deficient phenols to establish a highly functionalized framework. Post-Passerini–Smiles transformations leveraged this strategic layout to provide a step-economical route to a complementary library of three-dimensional spirooxindole hybrids derived from the PS adducts. This study reinforces the relevance of combining structural hybridization with multicomponent reaction strategies in the discovery of potential anticancer active pharmaceutical ingredients (APIs). Both libraries were evaluated against six human solid-tumor cell lines, including non-small cell lung carcinoma, cervical and colon adenocarcinoma, and breast and pancreatic cancers. The most active compound 4gaa exhibited GI₅₀ values below 10 μM for most of the tested cancer cell lines. Full article

The vitamin D receptor (VDR) has been implicated in tumor progression, but its functional role in pancreatic ductal adenocarcinoma (PDAC) metastasis remains unclear. Here, using pharmacological modulation, gain- and loss-of-function approaches, transcriptomic profiling, and an experimental lung colonization model, we demonstrate that VDR acts as a suppressor of PDAC metastasis. Pharmacological activation of VDR by calcipotriol did not affect tumor cell proliferation but markedly inhibited the migratory and invasive capacities of multiple PDAC cell lines. In contrast, genetic deletion or pharmacological inhibition of VDR significantly enhanced metastatic phenotypes. To investigate the underlying mechanisms, we performed RNA sequencing on PDAC cells with differential VDR expression following calcipotriol treatment. Pathway enrichment analysis identified MAPK/ERK signaling as one of the most prominently altered pathways upon VDR activation. Functional studies further demonstrated that ERK inhibition abrogated the pro-metastatic effects induced by VDR loss or inhibition. In vivo lung colonization assays confirmed that VDR deficiency markedly promoted pulmonary metastatic colonization. Collectively, these findings identify VDR as a critical suppressor of PDAC cell metastatic colonization and reveal a previously unrecognized VDR–ERK regulatory axis that may represent a potential therapeutic target for limiting metastatic progression in pancreatic cancer. Full article

Background: Mucinous adenocarcinoma (MAC) of the colorectum is a biologically distinct histological subtype whose prognostic significance may vary substantially according to primary tumor location. The impact of anatomical site on clinicopathological characteristics and long-term survival in MAC remains incompletely characterized. This study aimed to evaluate the influence of tumor location on oncological outcomes in patients with mucinous colorectal cancer using a large population-based dataset. Methods: Patients diagnosed with mucinous colorectal adenocarcinoma between 2000 and 2023 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Operated patients were stratified by anatomical location into three groups: right colon (cecum, ascending colon, hepatic flexure, transverse colon), left colon (splenic flexure, descending colon, sigmoid colon, rectosigmoid junction), and rectum. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Survival analyses were performed using the Kaplan–Meier method with log-rank testing. Multivariable Cox proportional hazards regression was used to assess the independent association of tumor location with survival outcomes, adjusting for age at diagnosis, year of diagnosis, sex, AJCC (American Joint Committee on Cancer) stage, tumor grade, receipt of radiotherapy and chemotherapy. Temporal trends in survival were evaluated across four consecutive diagnostic periods: 2000–2005, 2006–2011, 2012–2017, and 2018–2023. Results: A total of 40,698 patients with mucinous colorectal cancer were identified, of whom 40,174 underwent cancer-directed surgery (right colon n = 25,317; left colon n = 10,408; rectum n = 4449). The right colon was the predominant site of disease (62.9%). Median age was highest in the right colon group (74.0 years) and lowest in the rectum (65.0 years), while female sex predominated in right-sided tumors (55.7%) and male sex in rectal tumors (61.1%). Chemotherapy and radiotherapy utilization were markedly higher in the rectal group (68.6% and 64.5%, respectively) compared with the right colon (28.8% and 1.1%). Median OS was equivalent in the right and left colon groups (87.0 months each) but declined to 80.0 months in the rectal group. All pairwise CSS comparisons were statistically significant (all p < 0.001). On multivariable analysis, using the right colon as reference, the adjusted hazard ratios for CSS were 1.33 (95% CI: 1.28–1.39) for the left colon and 1.45 (95% CI: 1.34–1.57) for the rectum (both p < 0.001). Despite receiving the highest rates of multimodal therapy, rectal MAC demonstrated the worst long-term CSS across all anatomical groups. Temporal analyses revealed consistent CSS improvements in right-sided and left-sided MAC over the study period, whereas rectal MAC showed a non-linear trajectory with a plateau in the most recent diagnostic cohort (2018–2023). Conclusions: Mucinous colorectal adenocarcinoma demonstrates substantial biological and prognostic heterogeneity according to anatomical tumor location. Right-sided MAC was the most prevalent subtype and exhibited superior cancer-specific survival despite older patient age and lower treatment intensity. Rectal MAC demonstrated the worst long-term outcomes despite high utilization of multimodal neoadjuvant therapy, consistent with the established reduced responsiveness of mucinous tumors to conventional chemoradiotherapy. These findings underscore the necessity of incorporating anatomical location and tumor biology into individualized risk stratification and therapeutic planning for patients with mucinous colorectal cancer. Full article

Aberrant glycosylation contributes to tumour progression and metastatic dissemination. Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) is involved in poly-N-acetyllactosamine synthesis, but its role in colon adenocarcinoma remains insufficiently characterised. This retrospective single-centre study evaluated B3GNT3 expression and its association with clinicopathological parameters using TCGA and CPTAC data, immunohistochemistry in 97 colon adenocarcinomas, Western blot analysis, and transmission electron microscopy. TCGA analysis showed no significant differences in B3GNT3 mRNA expression between normal and tumour tissues. In contrast, CPTAC, immunohistochemistry, and Western blot analyses demonstrated increased B3GNT3 protein expression in tumour tissue compared with non-neoplastic mucosa. Immunohistochemical expression was assessed semi-quantitatively using the immunoreactive score (IRS). Lower B3GNT3 expression was associated with advanced stage and node-positive status. Because pathological stage and lymph node status are interrelated clinicopathological variables in colon adenocarcinoma, these findings were interpreted as partially overlapping associations rather than independent biological endpoints. Exploratory ROC and logistic regression analyses supported these cohort-level associations; however, the ROC-derived IRS cut-off was not externally validated, and regression models were interpreted cautiously. TEM/immunogold analysis supported Golgi/secretory-pathway localisation but was descriptive. Overall, B3GNT3 expression was associated with clinicopathological features in this retrospective cohort. Full article

Analysis of microbial abundance profiles offers significant potential for improving cancer prediction and candidate biomarker discovery. This study aimed to identify cancer-associated microbial biomarkers across five gastrointestinal (GI) cancers: head and neck, esophagus, stomach, colon, and colorectal cancers by analyzing tissue and blood samples from the TCMA dataset in parallel. A novel machine learning model, MicrobiomeGSM, was developed to enhance biological interpretability and reduce computational complexity through a taxonomic grouping strategy. Classification performance of MicrobiomeGSM was rigorously evaluated using a Random Forest Classifier with 100-fold Monte Carlo Cross-Validation. MicrobiomeGSM model effectively identified colon adenocarcinoma (COAD) using a set of 30 genus-level species, achieving a 97% AUC and 97% specificity. Comparative analysis was also performed with six traditional feature selection (TFS) algorithms; CMIM, mRMR, FCBF, IG, XGB, and SKB. Comparison of MicrobiomeGSM with TFS methods showed that while TFS methods capture statistical patterns, MicrobiomeGSM effectively leverages biological structures to identify clinically relevant candidate biomarkers. Also, MicrobiomeGSM competes with TFS methods in the analysis of high-dimensional datasets. In conclusion, these findings demonstrate that incorporating microbial abundance profiles with their taxonomic information into machine learning improve the interpretability and effectiveness of microbiome-based candidate biomarker discovery and may support future precision oncology application. Full article

Background: Adjuvant therapy decisions for T3N0 stage II colon cancer remain controversial. This study evaluates long-term outcomes, recurrence patterns, and conditional relapse-free survival (RFS) in pathologic T3N0 colon cancer. Methods: This retrospective study included 306 patients undergoing curative resection for T3N0 colonic adenocarcinoma (1995–2020). Early recurrence was defined as recurrence or death within 3 years after surgery. Survival was estimated via Kaplan–Meier. Cox regression, adjusted for treatment eras, evaluated survival factors. Inverse Probability of Treatment Weighting (IPTW) minimized selection bias. Conditional RFS utilized a 5-year landmark analysis. Results: Over a 133-month median follow-up, 72 patients (23.5%) recurred. Most recurrences (81.9%) occurred within 3 years; only 9.7% after 5 years. Five- and 10-year OS rates were 80.9% and 70.4%. Inadequate lymph node dissection (<12 nodes) was performed in 29.7% of the entire cohort and was found to be an independent adverse prognostic factor for OS. Adjuvant chemotherapy lacked overall OS benefit, though IPTW analysis suggested potential benefit in patients with inadequate dissection. Conditional RFS (5–10 years) for patients recurrence-free at 60 months was 95.0%. Exploratory analyses showed descriptive differences in post-relapse survival based on the clinical triggers prompting radiological evaluation (marker-triggered versus symptom-triggered presentations). Conclusions: T3N0 colon cancer recurrences occur predominantly within the first 3–5 years after surgery. Inadequate lymph node dissection is the primary adverse prognostic factor. Although a 5-year follow-up period appears adequate for most patients, individualized extended surveillance may be considered for selected high-risk patients. Adjuvant treatment and follow-up strategies should be tailored according to surgical quality and risk factors. Full article

Background: Colorectal neuroendocrine carcinomas (NECs), including small cell (SCNEC) and large cell (LCNEC) subtypes, are rare but aggressive malignancies with limited population-level data. Moreover, prior studies have limited stratification by histologic subtype and anatomic location, despite evidence of disease heterogeneity in colorectal malignancies. This study aimed to characterize the clinical characteristics, treatment patterns, and outcomes of colorectal NEC by histologic subtype and tumor location, and to compare them with neuroendocrine tumors (NETs) and adenocarcinomas (ACs). Methods: A retrospective cohort review was conducted utilizing the SEER database from 2000 to 2022 to identify patients with colorectal SCNEC, LCNEC, NET, and AC. Demographic, clinical, therapeutic and survival data were analyzed and compared using Kaplan–Meier methods, log-rank tests, and Cox proportional hazards regression. Results: A total of 790 SCNEC, 498 LCNEC, 31,200 NET, and 638,898 AC cases were identified. SCNEC and LCNEC were associated with advanced stage at diagnosis (66% and 55% stage IV, respectively) and inferior survival outcomes compared to NET and AC (median OS (mOS) of 7 and 8 months for SCNEC and LCNEC, respectively, p = 0.0002). Stratified by location, colonic SCNEC had the poorest survival (mOS 5 months), worse than rectal SCNEC (mOS 9 months); this pattern was not observed in LCNEC. Surgical resection was associated with improved OS in both NEC subtypes (HR range 0.25–0.56, all p < 0.012). Radiation therapy was associated with improved survival in NEC overall (SCNEC HR 0.58; LCNEC HR 0.71, both p < 0.05), with the observed benefit appearing greatest in rectal NEC. Demographic factors were associated with survival in NET and AC but had no significant impact in NEC. Conclusions: Colorectal SCNEC and LCNEC are highly aggressive malignancies with poor outcomes, with SCNEC demonstrating modestly inferior outcomes compared to LCNEC. This study demonstrates that both histologic subtype and anatomic site of disease are important determinants of prognosis and treatment response. This supports the concept that colorectal NEC represents a biologically heterogeneous disease, with colonic SCNEC showing the worst outcomes and rectal NEC associated with a potential enhanced response to radiation. These findings support the need for further prospective and molecular studies to better define treatment approaches and targeted therapies for these rare malignancies. Full article

Background: Brain metastasis is associated with poor prognosis in lung adenocarcinoma (LUAD). Anoikis resistance may contribute to tumor cell survival during metastatic dissemination and brain colonization; however, robust biomarkers for prognostic stratification and brain metastasis-associated classification remain limited. This study aimed to investigate anoikis-related molecular features in LUAD brain metastasis and develop a machine learning-based signature for prognostic assessment and exploratory classification of primary and brain-metastatic LUAD samples. Methods: We integrated single-cell and multi-cohort bulk transcriptomic data. Single-cell analysis was performed to characterize anoikis-related cellular states and intercellular communication in primary and brain-metastatic LUAD samples. In the bulk transcriptomic analysis, TCGA-LUAD was used for prognostic feature selection and risk-model construction, and GSE26939 was used for external prognostic validation. The classification performance of the fixed signature for distinguishing primary LUAD from brain-metastatic LUAD samples was further evaluated in GSE161116 and GSE271259. Immune microenvironment features were assessed, and an LLM-assisted exploratory drug-screening strategy combined with molecular docking was used to prioritize candidate compounds. Results: Single-cell analysis suggested that metastatic epithelial cells exhibited enhanced anoikis-related activity, accompanied by macrophage-associated SPP1-CD44 and MIF-(CD74+CXCR4) communication patterns. Machine learning-based feature selection identified an eight-gene signature consisting of BIRC3, CCL20, CLEC7A, CTSL, GOLM1, ICAM3, MTUS1, and SERPINH1. The signature showed prognostic value in TCGA-LUAD and GSE26939 and demonstrated exploratory classification performance in distinguishing primary LUAD from brain-metastatic LUAD samples. High-risk patients exhibited immune microenvironment alterations and enrichment of tumor progression-related pathways. LLM-assisted compound prioritization and molecular docking highlighted resveratrol and SB431542 as hypothesis-generating candidates with predicted interactions with core targets. Conclusions: This study identified an anoikis-related eight-gene signature for LUAD prognostic stratification and exploratory brain metastasis-associated classification. The findings suggest the potential involvement of anoikis-related tumor–microenvironment interactions in LUAD brain metastasis and provide candidate genes and compounds for further experimental validation. Full article

Background/Objectives: Mucinous adenocarcinoma (MAC) is a rare and clinically problematic subtype of rectal cancer, tending to present at an advanced stage and to respond poorly to neoadjuvant therapy. The consistently worse prognosis than that of not-otherwise-specified adenocarcinoma (NOS-AC) is not fully understood, potentially owing to intrinsically more aggressive biology or specific immune evasion mechanisms. We used the IMMUNOREACT multicentre cohort, with external validation in TCGA, to investigate the clinical and immunological features of rectal MAC in detail. Methods: Two hundred patients with rectal adenocarcinoma (16 MAC, 184 NOS-AC) from the IMMUNOREACT 1 (NCT04915326) and IMMUNOREACT 2 (NCT04917263) prospective cohorts were included. To account for the imbalance in baseline characteristics, propensity score matching (PSM) was performed on age, sex, neoadjuvant treatment and TNM stage. The immune microenvironment was characterised using immunohistochemistry (CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, PMS2, CD80), flow cytometry and NanoString PanCancer IO 360™ transcriptomics of adjacent healthy mucosa. Findings were externally validated against TCGA rectal and colon adenocarcinoma datasets. Results: MAC presented at significantly more advanced stage than NOS-AC across all TNM parameters: higher T stage (p = 0.006), N stage (p < 0.001), M stage (p = 0.039) and overall TNM stage (p < 0.001). In the unmatched cohort, MAC was associated with worse overall survival (HR 2.53; 95% CI 1.03–6.23; p = 0.043) and disease-free survival (HR 2.86; 95% CI 1.25–6.55; p = 0.013), but both differences became non-significant after PSM. MAC patients had higher haemoglobin after adjusting for confounders (mean difference [MD] 1.26 g/dL, 95% CI 0.30–2.31, p = 0.012), consistent with a hypothesis of reduced chronic rectal bleeding as a possible mechanism for late presentation. Transcriptomically, MAC showed suppression of HLA class II antigen presentation genes (HLA-DQA1, HLA-DQB1, HLA-DRB1) and myeloid activation genes (S100A8/A9/A12) in adjacent healthy mucosa. Loss of MMR proteins MSH6 and PMS2 in histologically normal mucosa was significantly more frequent in MAC. These findings were replicated in the TCGA cohort, which also showed lower tumour mutational burden and a distinct mucin-associated transcriptomic profile in MAC. Conclusions: The worse outcomes of rectal MAC appear to be driven largely by late-stage presentation, possibly owing to later diagnosis. MAC nonetheless carries a distinct immune phenotype, detectable even in histologically normal surrounding mucosa, that likely contributes to its treatment resistance. These observations provide a basis for developing histotype-specific approaches to both early detection and treatment in this uncommon but clinically challenging tumour subtype. Full article

Background/Objectives: The prognostic significance of mucinous colorectal adenocarcinoma (MAC) is controversial. Some studies report good outcomes relative to conventional colorectal adenocarcinoma (CRC) as is similarly described for MACs in, e.g., the breast, lung, pancreas and prostate. However, other studies refute this, proclaiming either no difference or worse outcomes. Herein, we proffer additional insights into the biology of MAC to explain these conflicting findings. Methods: A literature search was undertaken using keywords pertaining to MAC. Archival cases from our database were analyzed to provide context for our findings. Main Findings: The unifying histologic feature of MACs is their >50% content of extracellular mucin, but they should not be viewed as a monolithic entity, as is commonly portrayed in databases. Instead, MAC is a heterogenous disease as defined by histologic and molecular phenotypes. For example, MACs arising from adenoma-like CRC have relatively good outcomes unlike those from traditional serrated adenomas. Likewise, other factors such as histologic grade (grade 1–3), genomics (e.g., BRAF, KRAS, TP53), microsatellite instability (MSI-H, MSI-L), consensus molecular subtypes (CMS1–CMS4), and mucin types (MUC2, MUC5AC) significantly influence prognosis. These pathophysiologic features, demographics (age and sex) and specific anatomic regions/topography (right/left colon/rectum) can be captured and used to improve prognostic stratification. Conclusions: In contrast to previous studies that largely demarcated MAC as a discrete entity, this paper shows the limitations of this approach by highlighting the various sub-entities comprising MAC. Recognition of this heterogeneity may help to inform future treatment algorithms. Full article

Lectins are carbohydrate-binding proteins, some of which exhibit significant anti-tumor activity. Siye is a lectin derived from the red alga Kappaphycus alvarezii that was previously discovered using an artificial intelligence-guided genome mining strategy and shown to exert cytotoxic effects against several human cancer cell lines, including breast adenocarcinoma HCC1937. Based on the presence of shared glycopatterns between breast and colon cancers, we hypothesized that Siye may also exhibit anti-tumor activity against colon cancer cells. The cytotoxic effect of Siye on human colon cancer HCT116 cells was evaluated using the CCK-8 assay. Apoptosis was assessed by flow cytometry with Annexin V-FITC/PI staining. Expression levels of apoptosis-related genes (Bax, Bcl-2, Casp3, Casp8, Casp9, and TP53) were determined by qRT-PCR. Competitive inhibition assays using mannan were performed to assess the role of cell surface glycan binding. Siye significantly reduced the viability of HCT116 cells in a dose-dependent manner, with an IC₅₀ value of 14.065 μg/mL (=0.488 μM). Flow cytometry revealed that Siye promoted both early and late apoptosis in HCT116 cells, whereas in HCC1937 cells, the effect was primarily on early apoptosis. Mechanistically, Siye significantly upregulated the expression of the pro-apoptotic genes Bax (p < 0.05) and Casp9 (p < 0.001) in HCT116 cells, while in HCC1937 cells, Casp9 expression was significantly increased (p < 0.001). Morphological changes, including cell rounding and agglutination, were observed within 4 h of Siye treatment in both cell lines and were attenuated by co-treatment with mannan, suggesting that Siye-induced morphological changes are associated with binding to cell surface glycans. This study suggests that the red algal lectin Siye exerts anti-tumor effects against colon cancer HCT116 cells by inducing caspase-associated apoptosis. The differential apoptotic response between HCC1937 and HCT116 cells suggests cell-type-specific mechanisms. These findings extend the known anti-tumor activity spectrum of AI-discovered red algal lectin Siye and provide a basis for further investigation of its glycan-associated cellular effects and marine drug discovery potential. Full article

Colon adenocarcinoma (COAD) is a common malignancy with substantial morbidity and mortality, and the identification of new therapeutic targets remains essential for improving patient outcomes. In this study, we investigated SHC SH2-domain binding protein 1 (SHCBP1) in COAD through two complementary components with distinct evidentiary scopes. The first component comprised expression profiling, prognostic and methylation analyzes, bioinformatic characterization, and functional validation in vitro and in vivo. The second component comprised exploratory computational analyses, including predicted interaction network analysis and structure-based virtual screening. Public databases were used to analyze SHCBP1 expression, prognosis, and promoter methylation status. Co-expression and functional enrichment analyses were performed to explore the biological context of SHCBP1. In vitro and in vivo experiments were then conducted to evaluate the effects of SHCBP1 knockdown on tumor growth. SHCBP1 was significantly upregulated in COAD and was associated with poor patient prognosis. Promoter hypomethylation may contribute to its increased expression. Bioinformatic analyses suggested that SHCBP1 is associated with DNA replication and cell-cycle-related pathways. Experimental studies demonstrated that SHCBP1 knockdown suppressed cell proliferation and tumor growth. In the exploratory computational component, predicted interaction network analysis and virtual screening prioritized several in silico candidate interactions and two compounds with favorable predicted binding scores. These computational findings require independent biochemical and cellular validation. Overall, our findings suggest that SHCBP1 may represent a candidate biomarker associated with COAD proliferation and unfavorable prognosis, as well as a putative molecular target that warrants further validation. Full article

Background and Clinical Significance: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. Skeletal muscle metastases are extremely rare and typically occur in advanced or poorly differentiated tumors. In selected oligometastatic cases, surgical excision can provide symptom relief and requires a multidisciplinary approach. Case Presentation: We report a 73-year-old female patient with colonic adenocarcinoma treated with right hemicolectomy and side-to-side mechanical anastomosis, followed by adjuvant CAPOX chemotherapy. The tumor was characterized by MSI-H (microsatellite instability-high) status. During adjuvant treatment (less than 6 months after surgery), she developed progressive right thigh pain, later diagnosed as an intramuscular skeletal muscle metastasis measuring approximately 16 × 13 × 8 cm. The patient underwent en bloc resection of the tumor, followed by adjuvant chemotherapy after metastasectomy. Upon disease progression, first-line chemotherapy in combination with targeted therapy (bevacizumab) was administered. Conclusions: Skeletal muscle metastases from colorectal adenocarcinoma are rare. This case emphasizes the importance of recognizing atypical metastatic patterns and suggests that, in selected oligometastatic cases, surgical excision combined with a multidisciplinary approach may improve symptom control and clinical outcomes. Full article

Background/Objectives: Whole-cell vaccines have demonstrated clinical potential in cancer treatment and recurrence prevention, yet their immunogenicity and dendritic cell (DC) activation remain suboptimal. This study aimed to evaluate whether a needle-free injector (NFI) could enhance the immunogenicity and antitumor efficacy of whole-cell tumor vaccines. Methods: Adaptive immune responses induced by NFI and traditional syringe injection (SYI) were compared following whole-cell vaccine administration. The morphology of vaccine fluid ejected by NFI and SYI was examined, and the effects on DC antigen uptake and activation were assessed. Antitumor efficacy was further evaluated in MC38 colon adenocarcinoma challenge models. Results: NFI administration elicited stronger antigen-specific adaptive immune responses than SYI. The high-velocity pressure generated by NFI resulted in fragmentation of whole-cell vaccine material, and this morphological alteration was associated with enhanced DC antigen uptake and activation. These immunological improvements corresponded with superior tumor suppression in MC38 models following NFI-delivered vaccination. Conclusions: NFI delivery enhances the immunogenicity and antitumor efficacy of whole-cell tumor vaccines. These findings suggest that needle-free injectors may serve as a simple and effective strategy to improve the performance of whole-cell cancer vaccines. Full article