Search Results (272)

Background: Pancreatic solid pseudopapillary neoplasms (SPNs) are rare exocrine tumours with predominance in young women. These tumours are of low malignant potential, become considerably large before causing symptoms and are associated with good prognosis. This study aimed to present and analyse clinicopathological features and surgical outcome of SPNs. Methods: A retrospective analysis of 22 patients who underwent pancreatic surgery for SPNs in a single high-volume surgical centre in 2014–2023 was performed. Results: SPN was the most frequent in females (n = 21, 95.45%) in a mean age of 34 ± 11.09 (18–55) years. Fourteen (63.64%) patients were asymptomatic, and eight (36.36%) presented with symptoms. The most common clinical symptom was abdominal pain (n = 7, 31.82%). The majority of tumours were located in the pancreatic body (n = 8, 36.36%), and most patients underwent distal pancreatectomy (n = 11, 50%). The median tumour size was 3.6 cm (IQR = 4.9; range: 1.3–14). The median duration of hospitalisation was 12.5 days, and the postoperative complication rate was 40.91%. R0 resection was achieved in 18 (81.82%) patients. Postpancreatectomy acute pancreatitis (PPAP) was the most common postoperative complication. No adjuvant therapy in any patient was needed. One-year overall survival (OS) equalled 100% and five-year OS reached 85%. None of the patients developed diabetes or signs of impaired pancreatic secretion in the follow-up period. Histopathology showed features like perineural invasion in 72.73% of cases, pseudocapsule (59.09%), haemorrhage (45.45%), vascular invasion (40.91%), mucosal metaplasia (40.91%), necrosis (31.82%), and calcification in the capsule (31.82%). Ki67 did not exceed 7%. In one case (4.55%), metastasis to a lymph node was found. Clinical suspicion agreed with histopathological results in only 10 (45.45%) cases. Conclusions: SPN most often occurs in young females. The majority of cases are asymptomatic accidental findings. The final diagnosis of SPN can be based just on analysis of histopathological examination results. Full article

Background/Objectives: Acinar-to-ductal metaplasia (ADM) refers to the dedifferentiation or transdifferentiation of pancreatic acinar cells. Recently, ADM has received considerable attention as a potential precursor of pancreatic tumours. Previous studies in mouse models identified tuft cells, chemosensory epithelial cells, in ADM and pancreatic intraepithelial neoplasia (PanIN), both considered precursor lesions of pancreatic ductal adenocarcinoma (PDAC), but not in PDAC. We examined the presence of tuft cells in human ADM and PanIN. Methods: We analysed tissue samples from 29 patients (16 women, 13 men; median age 74 years) who underwent surgical resection for pancreatic tumours. Immunohistochemical staining for the tuft cell marker, POU2F3, was used to detect tuft cells in ADM and PanIN lesions. Results: ADM was present in all patients. POU2F3-positive tuft cells were observed in 46.4% of ADM lesions (327/705) but not in normal pancreatic acini. The number of POU2F3-positive tuft cells per PanIN area were significantly higher in low-grade PanIN (median, 2 cells; range, 0–20 positive cells) than in high-grade PanIN (median, 0 cell; range 0–4 positive cells) (p = 0.0050). The percentage of POU2F3-positive tuft cells per total cells in low-grade PanIN lesions (median, 1.1%; range 0–2.5%) was also significantly higher than that in high-grade PanIN lesions (median, 0%; range 0–1.1%) (p = 0.0044). Conclusions: Our results suggest that tuft cells emerge in human pancreatic acini during ADM, possibly as part of tissue repair following injury. Full article

Background: Boiling histotripsy (BH) uses high-amplitude, short-pulse focused ultrasound to disrupt tissue mechanically. Oncolytic virotherapy using reovirus has shown modest clinical benefit in pancreatic cancer patients. Here, reovirus and BH were used to treat pancreatic tumours, and their effects on the immune transcriptome of these tumours were characterised. Methods: Orthotopic syngeneic murine pancreatic KPC tumours grown in immune-competent subjects, were allocated to control, reovirus, BH and combined BH and reovirus treatment groups. Acoustic cavitation was monitored using a passive broadband cavitation sensor. Treatment effects were assessed histologically with hematoxylin and eosin staining. Single-cell multi-omics combining whole-transcriptome analysis with the expression of surface-expressed immune proteins was used to assess the effects of treatments on tumoural leukocytes. Results: Acoustic cavitation was detected in all subjects exposed to BH, causing cellular disruption in tumours 6 h after treatment. Distinct cell clusters were identified in the pancreatic tumours 24 h post-treatment. These included neutrophils and cytotoxic T cells overexpressing genes associated with an N2-like and an exhaustion phenotype, respectively. Reovirus decreased macrophages, and BH decreased regulatory T cells compared to controls. The combined treatments increased neutrophils and the ratio of various immune cells to Treg. All treatments overexpressed genes associated with an innate immune response, while ultrasound treatments downregulated genes associated with the transporter associated with antigen processing (TAP) complex. Conclusions: Our results show that the combined BH and reovirus treatments maximise the overexpression of genes associated with the innate immune response compared to that seen with each individual treatment, and illustrate the anti-immune phenotype of key immune cells in the pancreatic tumour microenvironment. Full article

Background: Pancreatic cancer is frequently identified as the cancer type with the shortest probable survival time after diagnosis, and efforts to develop successful treatments have had a very limited impact in the clinic. One reason for the limited therapeutic options is the lack of appealing drug targets. The great majority of pancreatic cancers are classified as Pancreatic Ductal Adenocarcinoma (PDAC), in which the genetic landscape is dominated by four genes: KRAS, TP53, CDKN2A, and SMAD4. However, despite extensive knowledge of these genetic drivers, the development of effective therapies has seen only very limited success. Methods: Existing evidence indicates that mutations in the tumour suppressor gene PTEN are uncommon in PDAC (<10% cases). However, the loss of PTEN function through non-genetic mechanisms may be much more common and have a strong impact. We therefore summarise and review a large body of immunohistochemical studies that address the loss of PTEN in PDAC as well as a smaller number of studies addressing other implicated proteins, including KDM6A and ARID1A. Results: These studies show some loss of PTEN protein in more than half of PDAC cases. Furthermore, although genetic changes in genes including KDM6A/UTX and ARID1A are also uncommon, reduced expression of their encoded proteins is observed in many, perhaps most, cases of PDAC. Conclusions: These analyses, which go beyond genetics, highlight the broader set of cellular functions that are dysregulated in many pancreatic cancers and provide broader opportunities for treatment strategies. This review highlights the emerging importance of other drivers in PDAC, which are less well-studied in this context. Full article

The incidence of pancreatic ductal adenocarcinoma (PDAC) is continuing to rise globally, while overall survival continues to be poor. Margin-negative (R0) surgical resection is essential to improve patient outcomes. With increasing understanding of the importance of anatomy and biology to establishing the resectability of PDAC, neoadjuvant therapy (NAT) has emerged as an important strategy to achieve an R0 resection, particularly for those with borderline resectable (BR-PDAC) and locally advanced disease (LA-PDAC). However, despite the multiple randomised controlled trials (RCTs) published in recent years, the optimum regime has yet to be fully established. The role of neoadjuvant chemoradiation therapy (CRT) remains controversial, possibly allowing for improved local disease control at a potential cost of interrupting systemic treatment. The emergence of stereotactic ablative radiotherapy (SABR), in place of conventional radiation therapy, improves patient tolerance of NAT and may improve local tumour control for patients with PDAC during limited fractions, minimising systemic therapy interruption. A particular niche for SABR may be as part of NAT for LA-PDAC, potentially converting a minority of patients with favourable biology to allow for resection. While pancreaticoduodenectomy can be technically challenging following NAT, there is no difference in the rate of major morbidity or mortality post operatively. Indeed, post-operative pancreatic fistula (POPF) rates may be lower following NAT. Overall, however, evidence for SABR in a neoadjuvant setting for BR- and LA-PDAC remains sparse. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is associated with poor prognosis. Despite years of research and improvements in chemotherapy regimens, the 5-year survival rate of PDAC remains dismal. Therapies for PDAC often face resistance owing in large part to an extensive desmoplastic stromal matrix. Modelling PDAC ex vivo to investigate novel therapeutics is challenging due to the complex tumour microenvironment and its heterogeneity in native tumours. Development of novel therapies is needed to improve PDAC survival rates, for which disease models that recapitulate the tumour biology are expected to bear utility. This review focuses on the existing preclinical models for human PDAC and discusses advancements in tissue remodelling to guide translational PDAC research. Further emphasis is placed on photodynamic therapy (PDT) due to the ability of this treatment modality to not only directly kill cancer cells by minimally invasive means, but also to perturb the tumour microenvironment and elicit a post-therapeutic anti-tumour immune response. Accordingly, more complex preclinical models that feature multiple biologically relevant PDAC components are needed to develop translatable PDT regimens in a preclinical setting. Full article

Cancer metabolism is a hallmark of cancer. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This study delves into the role of glucagon, as a component of the pancreatic microenvironment, in regulating features of pancreatic neuroendocrine tumour (pNET) cells and the metabolic remodelling occurring in the presence and absence of glucose. pNET cell lines (BON-1 and QGP-1) and the non-malignant pancreatic α-TC1 cell line were used as models. Results showed that pNET cells responded differently to glucose deprivation than α-TC1 cells. Specifically, pNET cells upregulated the GCGR in the absence of glucose, while α-TC1 cells did so in high-glucose conditions, allowing the glucagon-related pERK1/2 activation under these conditions in pNET cells. Glucagon enhanced cancerous features in pNET BON-1 cells under glucose-deprived and hyperglucagonemia-compatible concentrations. In the α-TC1 cell line, glucagon modulated cell features under high-glucose and physiological glucagon levels. NMR exometabolome analysis revealed differences in metabolic processes based on glucose availability and glucagon stimulation across cell lines, highlighting amino acid metabolism, glycolysis, and gluconeogenesis. The expression of metabolic genes was consistent with these findings. Interestingly, QGP-1 and α-TC1 cells produced glucose in no-glucose conditions, and glucagon upregulated glucose production in α-TC1 cells. This suggests that gluconeogenesis may be beneficial for some pNET subsets, pointing out novel metabolism-based strategies to manage pNETs, as well as a step forward in endocrinology and systemic metabolism. The association between GCGR expression and malignancy and a negative correlation between glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) expression was observed, indicating a biological role of glucagon in pNETs that deserves to be explored. Full article

Pancreatic cancer involving the porto-mesenteric junction (PMJ) represents a challenge to pancreatic surgeons. Restoring mesenteric venous drainage is an essential component of vascular reconstruction after tumour resection. In contrast, management of the splenic venous drainage can involve the ligation or reconstruction of the splenic vein (SV). Evidence suggests that splenic vein ligation (SVL) is commonly associated with sinistral portal hypertension (SPH), especially if multiple venous tributaries were divided to facilitate resection. Although the association between SVL and SPH is well documented, the risk of symptomatic SPH is not widely reported, presumably due to the low incidence and poor survival of pancreatic cancer patients. Splenic vein reconstruction (SVR) has been proposed to decrease the risk of SPH but is fraught with technical complexity and increased morbidity. Moreover, SVR does not guarantee the prevention of SPH, as patency rates vary and associated hemodynamic changes are unpredictable. Patient selection and the surgical expertise available can guide SV intraoperative management, taking into consideration the risks and benefits associated with each approach. A comprehensive review of the current literature highlighting the incidence and clinical impact of SPH after the resection of pancreatic cancer involving the PMJ is presented. Full article

The Wnt signalling pathway plays a crucial role in tissue homeostasis and cancer biology due to its regulation of cellular processes, including proliferation, migration, and stem cell activity. Frizzled receptor 7 (FZD7) (a member of the F-class G protein-coupled receptors) has emerged as a key Wnt receptor within this pathway, which is elevated in several human malignancies. FZD7 is notably upregulated in gastrointestinal, breast, pancreatic, and hepatocellular carcinomas and transmits oncogenic Wnt signalling through canonical and non-canonical pathways. FZD7 promotes tumour initiation, and emerging evidence implicates FZD7 in cancer stem cell maintenance and epithelial–mesenchymal transition (EMT), reinforcing its role in metastasis. Therapeutic strategies targeting FZD7 have shown promise, including FZD7-specific monoclonal antibody-drug conjugates (ADCs), human single-chain fragment variable (scFVs) antibodies, and nanoparticles. Notably, our recent development of FZD7-ADC has demonstrated tumour-selective cytotoxicity with reduced off-target effects, positioning FZD7 as an attractive therapeutic target. Additionally, nanoparticle-based drug delivery systems have enhanced the precision of existing chemotherapies by targeting FZD7-expressing tumour cells. Despite significant advances, clinical translation remains a challenge due to potential on-target toxicity and the complexity of tumour microenvironments. Future research should focus on optimising delivery systems, refining antibody specificity, and conducting comprehensive preclinical and clinical trials. This review will focus on novel discoveries regarding FZD7 in cancer and provide an update on our original review on this subject in 2016. Additionally, we present new figures generated by our group using the publicly available Pan-Cancer Atlas RNAseq datasets, highlighting FZD7 expression patterns in patient samples. This integrated approach aims to provide updated insights into the function of FZD7 during cancer and its growing status as an attractive target for therapy. In summary, FZD7 stands out as a promising molecular target in cancer therapy due to its selective overexpression in tumours, functional role in Wnt-driven oncogenesis, and potential for innovative therapeutic applications. This review underscores the critical need for the continued exploration of FZD7-targeted therapies to improve patient outcomes in cancer treatment. Full article

Background/Objectives: CAR T cell therapy, as a rapidly advancing immuno-oncology modality, has achieved significant success in the treatment of leukaemia and lymphoma. However, its application in solid tumours remains limited. The challenges include the heterogeneity of tumours, local immunosuppression, poor trafficking and infiltration, life-threatening toxicity and the lack of precise representative immunocompetent research models. Considering its typically dense and immunosuppressive tumour microenvironment (TME) and early metastasis, pancreatic ductal adenocarcinoma (PDAC) was employed as a model to address the challenges that hinder CAR T cell therapies against solid tumours and to expand immunotherapeutic options for advanced disease. Methods: A novel murine A20FMDV2 (A20) CAR T cell targeting integrin αvβ6 (mA20CART) was developed, demonstrating efficient and specific on-target cytotoxicity. The mA20CART cell as a monotherapy for orthotopic pancreatic cancer in an immunocompetent model demonstrated modest efficacy. Therefore, a novel triple therapy regimen, combining mA20CART cells with oncolytic vaccinia virus encoding IL-21 and a TGF-β-blocking antibody was evaluated in vivo. Results: The triple therapy improved overall survival, improved the safety profile of the CAR T cell therapy, attenuated metastasis and enhanced T cell infiltration. Notably, the potency of mA20CART was dependent on IL-2 supplementation. Conclusions: This study presents an αvβ6-targeting murine CAR T cell, offering a novel approach to developing CAR T cell technologies for solid tumours and a potential adjuvant therapy for pancreatic cancer. Full article

Background: Despite the development of advanced cancer therapies, achieving cancer eradication remains challenging. Radioimmunotherapy (RIT) is an innovative approach that combines radionuclides with monoclonal antibodies targeting tumour-associated antigens or those expressed by the tumour microenvironment. Over the past two decades, RIT has been extensively researched, along with two RIT products—⁹⁰Y-ibritumomab tiuxetan and ¹³¹I-tositumomab. However, despite its demonstrated efficacy in non-solid tumours, RIT’s clinical use remains limited, and its effectiveness in solid tumours is inconclusive. This study aimed to analyse randomised controlled trials (RCTs) to evaluate the overall clinical effectiveness of RIT across different cancer types and its impact on treatment outcomes. Methods: A systematic search of PubMed, EMBASE, Scopus, CENTRAL, and Google Scholar was conducted from January 2000 to October 2024 in accordance with PRISMA guidelines and the PICOS framework. Studies were included if they were RCTs evaluating RIT for cancer treatment and reported treatment outcomes such as overall survival (OS), progression-free survival (PFS), disease-free survival, or time to progression (TTP). Data extraction was performed using a standardised Excel form, and study quality was assessed with the Joanna Briggs Institute Critical Appraisal Tool for RCTs. A narrative synthesis of the data was complemented by meta-analyses where feasible, particularly for progression- and survival-related endpoints. Results: Out of 2241 records identified, 20 RCTs encompassing approximately 3562 patients were included. The majority of trials focused on non-solid tumours, particularly non-Hodgkin’s lymphoma (NHL), while a smaller subset evaluated solid tumours such as lung, pancreatic, ovarian, and prostate cancers. Most non-solid tumour studies employed ⁹⁰Y-ibritumomab tiuxetan or ¹³¹I-tositumomab, targeting the CD20 antigen, whereas limited evidence exists for RIT efficacy in solid tumours. Meta-analysis of progression-related outcomes yielded a pooled hazard ratio (HR) of 0.48 (95% CI: 0.39–0.59), indicating a 52% reduction in the risk of progression. In contrast, overall survival outcomes were more variable, with a pooled OS HR of 0.80 (95% CI: 0.60–1.07). Adverse events, predominantly haematological and nonhaematological toxicities, were common yet generally reversible. The findings suggest that RIT, especially when used as part of combination regimens, significantly improves treatment outcomes in non-solid tumours but has an inconsistent effect in solid tumour settings. Conclusions: The results underscore the clinical promise of RIT in treating non-solid tumours like NHL, where combination regimens yield superior outcomes compared to monotherapy. However, the inconclusive evidence in solid tumours highlights the need for further large-scale, well-designed RCTs to define the optimal use, dosing, and patient selection for RIT in these settings. Additionally, standardisation in outcome reporting and longer follow-up periods are essential for more accurate economic and clinical assessments. Overall, RIT represents a valuable therapeutic modality, yet its integration into cancer treatment regimens should be guided by further research aimed at mitigating toxicity and optimising combination strategies. Full article

Background: Pancreatoduodenectomy with venous resection (PDVR) may be performed to achieve tumour clearance in patients with a pancreatic ductal adenocarcinoma (PDAC) with venous involvement. This study aimed to evaluate the impact of PDVR on PDAC outcomes. Methods: In total, 435 PDAC patients with either R0 status (n = 322) or R1 status within the superior mesenteric vein groove (n = 113) were extracted from the Recurrence After Whipple’s (RAW) study dataset. PDVR patients were matched in a 1:2 ratio with standard PD patients. Comparisons were then made between the two groups (surgical radicality and survival). Results: A total of 81 PDVRs were matched with 162 PDs. Neoadjuvant chemotherapy (5.7% vs. 13.6%, p = 0.032) and R1 resection rates (17.9% vs. 42%, p < 0.001) were higher in the PDVR group. Risk factors for R1 resection included venous resection (p < 0.001 for sleeve and p = 0.034 for segmental resection), pT3 (p = 0.007), and pN1 stage (p = 0.045). PDVR patients had lower median overall survival (OS, 21 vs. 30 months (m), p = 0.023) and disease-free survival (DFS, 17 m vs. 24 m, p = 0.043). Among PDVR patients, R status did not impact on OS (R0: 23 m, R1: 21 m, p = 0.928) or DFS (R0: 18 m, R1: 17 m, p = 0.558). Irrespective of R status, systemic recurrence was higher in the PDVR group (p = 0.034). Conclusions: Independent of R status, the PDVR group had lower overall survival and higher systemic recurrence rates. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, often associated with new-onset diabetes. The relationship between PDAC and diabetes, particularly type 3c diabetes, remains poorly understood. This study investigates whether PDAC-associated diabetes represents a distinct subtype by integrating transcriptomic and histological analyses. Whole-tumour RNA sequencing data from The Cancer Genome Atlas (TCGA) were analysed to compare gene expression profiles between PDAC patients with and without diabetes. Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) deconvolution was employed to assess immune cell populations. Histopathological evaluations of pancreatic tissues were conducted to assess fibrosis and islet morphology. Histological analysis revealed perivascular fibrosis and islet basement membrane thickening in both PDAC cohorts. Transcriptomic data indicated significant downregulation of islet hormone genes insulin (INS) and glucagon (GCG) but not somatostatin (SST) in PDAC-associated diabetes, consistent with a type 3c diabetes phenotype. Contrary to previous reports, no distinct immunogenic signature was identified in PDAC with diabetes, as key immune checkpoint genes (Programmed Cell Death Protein 1 (PDCD1), Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), Programmed Death-Ligand 1(PD-L1)) were not differentially expressed. The findings suggest that PDAC-associated diabetes arises through neoplastic alterations in islet physiology rather than immune-mediated mechanisms. The observed reductions in endocrine markers reinforce the concept of PDAC-driven β-cell dysfunction as a potential early indicator of malignancy. Given the poor response of PDAC to PD-L1 checkpoint inhibitors, further research is needed to elucidate alternative therapeutic strategies targeting tumour–islet interactions. Full article

Radiolabelled fibroblast activation protein inhibitor (FAPI) tracers have the potential to overcome the limitations of 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) and improve the diagnosis and staging of hepato-pancreato-biliary (HPB) cancers. This study aims to compare the diagnostic performance of radiolabelled FAPI versus [¹⁸F]FDG PET imaging in HPB cancers. A systematic search of PubMed, Embase, Web of Science and Cochrane Library was performed to identify eligible studies on the diagnostic performance of FAPI PET for primary HPB tumours (hepatocellular carcinoma (HCC), pancreatic cancer (PC) and biliary tract cancer (BTC)) and for liver metastases of gastrointestinal origin. The diagnostic performance was defined as a combination of detection rate and semi-quantitative tracer uptake. A random-effects model was used to calculate the risk differences. In total, 28 studies were included. Histopathology was the reference standard for the primary tumour in 26 studies (93%). The detection rate of radiolabelled FAPI in comparison to [¹⁸F]FDG was significantly higher in HCC (0.33, 95% CI: 0.20–0.47 and 0.34, 95% CI: 0.23–0.45) and BTC (0.27, 95% CI: 0.11–0.43 and 0.28, 95% CI: 0.08–0.48), in the patient- and lesion-based analyses, respectively. In PC, no differences were observed. Radiolabelled FAPI outperformed [¹⁸F]FDG in the lesion-based detection of lymph node, liver and extra-hepatic metastases. In all HPB cancers, the mean SUVmax was significantly higher with radiolabelled FAPI compared to [¹⁸F]FDG. Molecular imaging with FAPI PET seems to have several benefits over [¹⁸F]FDG PET in HPB cancer diagnostics, with an overall higher tracer uptake, and higher detection rates in HCC and BTC. Full article

Gracilaria species, a widely distributed genus of red macroalgae, have gathered significant attention for their diverse medical applications attributable to their bioactive sulphated polysaccharides (SPs). This review examines the global narrative of various Gracilaria SP applications in terms of their therapeutic potential and mechanistic insights into the use of these SPs against a range of medical conditions, including cancer, inflammation, neurodegenerative disorders, diabetes, and immune dysfunctions. SPs extracted from G. lemaneiformis and G. fisheri have demonstrated potent anti-tumour activities by inducing apoptosis through various mechanisms, including the upregulation of CD8⁺ T cells and IL-2, inhibition of EGFR/MAPK/ERK signalling pathways, and activation of the Fas/FasL pathway. Selenium nanoparticles (SeNPs) conjugated with SPs further enhanced the targeted delivery and efficacy of these SPs against glioblastoma by the downregulation of ROS followed by the activation of p53, MAPK, and AKT pathways. The anti-inflammatory properties of SPs are evidenced by key suppressive inflammatory markers like NO, TNF-α, IL-1β, and IL-6 in mutant rodent models. SPs from G. cornea and G. birdiae effectively reduce neutrophil migration and vascular permeability, offering potential treatments for acute inflammation and conditions such as colitis by modulating pathways involving COX-2 and NF-κB. Neuroprotective effects by SPs (from G. cornea and G. gracili) studied in 6-OHDA-induced rats, which mitigate oxidative stress and enhance neuronal cell viability, facilitate the management of neurodegenerative diseases like Parkinson’s and Alzheimer’s. Regarding the hypoglycaemic effect, SPs from G. lemaneiformis exhibit a glucose-modulating response by improving insulin regulation, inhibiting α-amylase activity, repairing pancreatic β-cells, and modulating lipid metabolism. Moreover, immunomodulatory activities of Gracilaria-derived SPs include the stimulation of macrophages, T-cell proliferation, and cytokine production, underscoring their potential as functional food and immunotherapeutic agents. Recently, Gracilaria-derived SPs have been found to modulate gut microbiota, promote SCFA production, and enhance gut microbials, suggesting their potential as prebiotic agents (G. rubra and G. lemaneiformis). This review highlights the multifaceted medical applications of Gracilaria sulphated polysaccharides, providing detailed mechanistic insights and suggesting avenues for future clinical translation and therapeutic innovations. Full article