The intestinal microbiota is an important part of the human body, and its composition can affect the effectiveness of immunotherapy. In the last few years, the modulation of intestinal microbiota in order to improve the effectiveness of immunotherapy has become a current topic in the scientific community, but there is a lack of research in this area. In this review, the goal was to analyze the current relevant literature related to the modulation of intestinal microbiota and the effectiveness of immunotherapy in the treatment of cancer. The effects of antibiotics, probiotics, diet, and fecal microbial transplantation were analyzed separately. It was concluded that the use of antibiotics, especially broad-spectrum types or larger quantities, causes dysbiosis of the intestinal microbiota, which can reduce the effectiveness of immunotherapy. While dysbiosis could be repaired by probiotics and thus improve the effectiveness of immunotherapy, the use of commercial probiotics without evidence of intestinal dysbiosis has not yet been sufficiently tested to confirm its safety for cancer for immunotherapy-treated cancer patients. A diet consisting of sufficient amounts of fiber, as well as a diet with higher salt content positively correlates with the success of immunotherapy. Fecal transplantation is a safe and realistic adjuvant option for the treatment of cancer patients with immunotherapy, but more clinical trials are necessary. Modulating the microbiota composition indeed changes the effectiveness of immunotherapy, but in the future, more human studies should be organized to precisely determine the types and procedures of microbiota modulation.

Background/Objectives: Immune checkpoint inhibitors (ICI) represent a significant breakthrough in cancer management, but they can cause adverse effects such as immune-mediated colitis (IMC). The standard first-line treatment is corticosteroids, and second-line treatment is infliximab or vedolizumab. However, a proportion of immune-mediated colitis (IMC) cases are refractory to immunosuppressive treatment, which has led to the exploration of novel approaches such as fecal microbiota transplantation. Methods: We present two patients who both developed grade III IMC following application of durvalumab and pembrolizumab, respectively. Both patients were refractory to corticosteroid therapy, while the first one also showed no improvement to infliximab. We performed two separate applications of FMT on both patients, from different donors, as a rescue treatment. Results: After unsuccessful immunosuppressive treatment and following rescue FMT, both patients demonstrated a rapid and sustained improvement in inflammatory markers, clinical symptoms, quality-of-life scores, and colonoscopy findings, without additional immunosuppressive treatment. Conclusions: FMT appears to be safe and a potentially effective treatment option for patients with refractory IMC both as second- and third-line therapy options. Continued efforts toward rigorous donor screening, use of standardized biobanks, and standardizing FMT protocols will further enhance safety and reproducibility.

Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but their use is frequently accompanied by immune-related adverse events, among which immune-mediated colitis (IMC) represents one of the most common and clinically significant gastrointestinal toxicities. IMC may lead to treatment interruption, increased morbidity, and compromised quality of life. This review aims to provide a comprehensive overview of the pathophysiology, risk factors, diagnosis, management, and emerging therapeutic strategies with particular emphasis on the role of the gut microbiota and fecal microbiota transplantation (FMT). Methods: This review integrates current international guidelines, meta-analyses, clinical trials, and recent translational studies addressing IMC. The available evidence on immunological mechanisms, predictive biomarkers, clinical presentation, diagnostic algorithms, and treatment options was critically synthesized to outline a structured and multidisciplinary management approach. Results: IMC is driven by dysregulated immune activation, cytokine release, and alterations in gut microbiota. Incidence and severity vary according to ICI class, combination regimens, tumor type, and patient-related factors. Diagnosis requires exclusion of infectious causes, laboratory assessment, and endoscopic and histologic evaluation with CTCAE-based severity grading. Corticosteroids remain the cornerstone of first-line therapy, while infliximab and vedolizumab are effective in steroid-refractory cases. Emerging therapies, including JAK inhibitors and FMT, have shown promising results in refractory disease. Conclusions: IMC is a complex and potentially severe complication of ICI therapy that necessitates early recognition, accurate grading, and individualized, multidisciplinary management. Severity-guided treatment, timely escalation to biologics, and careful balancing of immunosuppression with antitumor efficacy are essential for optimal outcomes. Future research should focus on biomarker validation, microbiome-targeted therapies, and prospective trials to refine therapeutic algorithms and define the optimal role and timing of FMT in clinical practice.

Background: Pancreatic adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited survival gains despite advances in systemic therapy. However, rapid expansion of biomarker-directed therapies, immunotherapy, and novel treatment modalities has created an increasingly complex clinical trial landscape. We aimed to characterize contemporary PDAC clinical development and identify emerging therapeutic trends. Methods: We performed a narrative review with a scoping approach of active PDAC clinical trials registered on ClinicalTrials.gov. Eligible studies were initiated between January 1, 2021, and February 16, 2026, and included recruiting, active, or not-yet-recruiting phase I–III trials. Data extracted included trial phase, disease setting, therapeutic strategy, endpoints, enrollment, sponsorship, and late-phase development. Results: A total of 355 interventional trials were included. Most trials were phase I, phase I/II, or phase II trials, with fewer than 10% being evaluated in phase II/III or phase III development. Advanced or metastatic disease was the predominant setting. Chemotherapy remained the most frequently incorporated treatment modality, while molecularly targeted therapies were evaluated in 167 trials. KRAS/RAS-directed approaches represented the largest targeted subgroup, although only daraxonrasib and setidegrasib reached phase III evaluation. Immunotherapy was evaluated in 139 trials, although only a limited number progressed to late-phase development, reflecting the immune-resistant biology of pancreatic adenocarcinoma. Additional areas of active investigation included Claudin 18.2-targeted therapies, MTAP-associated approaches, homologous recombination deficiency-directed strategies, CD73 inhibition, radiotherapy, local interventions, surgery-focused optimization, imaging-guided approaches, and supportive-care interventions. Industry organizations were listed as the lead sponsor for approximately half of all studies, while non-commercial organizations supported most remaining trials. Conclusions: The contemporary PDAC clinical trial landscape is characterized by broad therapeutic diversification but limited late-phase maturity. Chemotherapy remains the dominant treatment backbone, whereas KRAS/RAS-directed therapies have emerged as the most advanced precision oncology strategy. Future progress will likely depend on successful integration of biomarker-selected therapies with established multidisciplinary treatment approaches, including optimized systemic therapy, local-control strategies, and supportive care.

Parallel to the increased use of immune checkpoint inhibitors (ICIs), the incidence of immune-related adverse events (irAEs) is also increasing. Almost all organs can be affected by the immune-mediated response, including the liver, pancreas and biliary tract. Immune-Mediated Hepatitis is a common complication of ICI therapy, while cholangitis, cholecystitis and pancreatic involvement are less frequent. Emerging evidence from clinical trials and real-world data series helps us better understand the risk factors, diagnostic challenges and management strategies for these irAEs. With wider use of ICIs, more data are also available on the management of special populations with comorbidities and patients with difficult-to-treat or treatment-resistant adverse events, but larger prospective studies and more robust evidence are required for further recommendations on their management and ICI reintroduction. In clinical practice, a multidisciplinary approach to the management of ICI-mediated complications is advised, with close collaboration among specialties such as oncologists, gastroenterologists or hepatologists, pathologists, radiologists and others. While Immune-Mediated Hepatitis is a common irAE of ICI therapy, pancreato-biliary involvement is often overlooked and underdiagnosed. These irAEs require multimodal management, development of new biomarkers and prediction models to facilitate decision-making and improve patient outcomes.