Immune-Related Adverse Events

1. To identify biomarkers of immune-related adverse events; 2. To develop a predictive model for immune-related adverse events.

This observational study aims to comprehensively characterize immune-related adverse events (irAEs) occurring during immune checkpoint inhibitor (ICI) therapy in cancer patients and to evaluate the safety and clinical outcomes of ICI rechallenge following irAE resolution. In addition to detailed clinical data collection, the study incorporates biospecimen acquisition, when clinically indicated and feasible, including peripheral blood and organ-specific specimens (e.g., bronchoalveolar lavage fluid for ICI-related pneumonitis, liver biopsy tissue for ICI-related hepatitis, and other relevant clinical specimens). These samples will support exploratory immunologic and molecular analyses to better understand mechanisms underlying irAE development, resolution, and recurrence after rechallenge. This study is designed to generate real-world evidence to improve risk stratification, toxicity management, and decision-making regarding immunotherapy continuation or re-initiation.

This study is a prospective, single-arm, phase II exploratory clinical trial. The primary endpoint of this study is to evaluate the pathological complete response (pCR) rate after surgery and to assess the safety of neoadjuvant therapy with adebrelimab combined with platinum-based chemotherapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) at the Second Qilu Hospital of Shandong University. The primary endpoint of this clinical trial is the pathological complete response (pCR) rate, defined as the absence of residual viable tumor cells in the resected specimen, including lymph nodes (ypT0N0M0). Secondary endpoints include the major pathological response (MPR) rate, objective response rate (ORR), treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs), as well as quality of life (QOL) assessments during neoadjuvant immunochemotherapy (nICT). MPR is defined as less than 10% residual viable tumor cells in the primary tumor bed following neoadjuvant therapy and resection. ORR represents the percentage of patients achieving complete response (CR) or partial response (PR). Other secondary measures include the tumor downstaging rate, surgery rate, R0 resection rate (defined as no residual tumor at the resection margins), and perioperative complication rate. Furthermore, overall survival (OS) and relapse-free survival (RFS) are considered exploratory endpoints in this study. By evaluating these diverse endpoints, the investigators aim to comprehensively assess the efficacy, safety, and overall impact of the nICT approach in patients with locally advanced resectable ESCC. Additionally, it is planned to construct 20 pairs of esophageal squamous cell carcinoma and adjacent normal esophageal squamous epithelial organoids, laying the groundwork for future in-depth exploration of the mechanisms underlying esophageal carcinogenesis and progression, as well as functional studies of specific genes.

Immune checkpoint inhibitors (ICIs) have transformed the treatment of solid tumors but are associated with immune-related adverse events (irAEs) that can affect virtually any organ system. While many irAEs are well recognized, neurological, neurocognitive, and psychiatric toxicities remain diagnostically challenging, potentially severe, and poorly understood, with limited predictive biomarkers. This prospective longitudinal observational cohort study enrolls adult patients with solid tumors initiating a new course of ICI therapy. Participants undergo standardized baseline clinical assessments and biospecimen collection prior to ICI initiation, followed by longitudinal follow-up and event-driven sampling. Patients are dynamically assigned to organ-specific irAE cohorts based on the first clinically significant irAE that dictates management. Patients without grade ≥2 irAEs during follow-up serve as a comparator control cohort. The primary objective is to characterize longitudinal immune and inflammatory biomarker trajectories associated with the development of irAEs and to identify predictive and prognostic biomarkers, with particular emphasis on neurological, neurocognitive, and psychiatric toxicities. Integrated clinical, imaging, and multi-omics data will be used to elucidate mechanisms of toxicity and inform future risk stratification and personalized management strategies.

This study aims to identify a way to predict the side effects that some people with cancer experience when receiving immunotherapy. These side effects, known as immune-related adverse events (irAEs), occur when the immune system mistakenly attacks healthy tissues, like certain autoimmune diseases. At present, clinicians lack reliable tests to determine who is most likely to develop these reactions. The goal of this study is to determine whether substances in the blood called interferons (IFNs) could serve as early warning markers. The study will include 300 people with cancer who are about to begin immunotherapy. To provide a meaningful comparison, the investigators will also enroll 40 individuals with autoimmune diseases such as lupus. Understanding how IFN levels differ between these groups may help clarify whether IFN patterns in cancer patients resemble those seen in autoimmune disease. Participants in both groups will be asked to provide small blood samples at predefined time points during their clinical care or treatment. Researchers will measure the levels of different IFN types in all samples to compare IFN levels between cancer patients and individuals with autoimmune diseases, and within the cancer group between patients who develop irAEs and those who do not. The long-term aim of the study is to develop a simple test that can help clinicians identify patients at higher risk of irAEs. Immune-related adverse events (irAEs) are a frequent complication in cancer patients treated with immune checkpoint inhibitors (ICIs), and they often resemble or exacerbate preexisting autoimmune diseases. Despite extensive research in the field, no validated predictive biomarkers of irAEs currently exist. Emerging evidence suggests that the IFN signature -long implicated in the pathogenesis of several systemic autoimmune diseases (SADs)- may also be upregulated in patients who develop ICI-induced irAEs, likely with substantial overlap among different IFN subtypes. Given these clinical and molecular similarities with SADs, it is plausible that IFN levels in peripheral blood carry predictive value for irAE risk, although the dominant IFN types in ICI-related toxicity remain unknown. The INTER-AUTENTIC project aims to determine whether baseline IFN levels and their dynamic changes, measured in peripheral blood using a dedicated panel, can predict the onset of irAEs in cancer patients receiving ICIs. Supported by the Medical Oncology departments of six university hospitals in Northern Spain, this multicenter, observational, prospective cohort study has been underway since 2021. Biobank samples have been collected from ICI-treated patients before treatment initiation, at protocol-defined time points, and at the moment of irAE diagnosis (ICI cohort). The study seeks to identify the IFN subtypes with the most pronounced differential expression between patients with and without irAEs, and to evaluate whether IFN levels enhance the predictive performance of a model incorporating other clinical variables potentially associated with immune-mediated toxicity. A sample size of 300 cancer patients has been estimated for this analysis. In addition, a second prospective cohort of 40 non-cancer patients with systemic lupus erythematosus, primary Sjögren's syndrome, systemic sclerosis, and/or idiopathic inflammatory myopathy (SAD cohort) will be included. Since IFNs play a well-established pathogenic role in these conditions, this cohort will allow characterization of the IFN signature at key follow-up points (baseline, remission, and disease flare) and comparison with the IFN profiles of ICI-treated patients, regardless of whether they develop irAEs.

This study evaluates the effectiveness of low-dose corticosteroids in managing grade 2-3 immune-related hepatitis in cancer patients treated with immune checkpoint inhibitors. It aims to determine whether of 0.5-1miligram per kilogram bodyweight prednisolone is sufficient to manage immune-related hepatitis without the need for dose escalation or additional immunosuppressive therapy.

Immunotherapies have improved cancer outcomes, but have a unique profile of immune-related adverse events (irAEs). Biorepositories have been established to collect data and samples to help improve our understanding of irAEs, however identifying patients who are eligible for these biorepositories in a timely fashion can be challenging. The goal of this study is to determine if an informatics system for automated irAE detection can improve registration to a prospective irAE biorepository (NCT04242095). The informatics system automatically "reads" participants' electronic health records (EHRs) and determines whether that patient may be experiencing an irAE. The main questions it aims to answer are: * Is it feasible to implement an informatics system for daily analysis of EHR data to detect irAEs? * Does the automated irAE detection system improve registration rates to an irAE biorepository at our institution following an eligible irAE? Researchers will compare standard irAE monitoring to informatics-assisted irAE monitoring to see if using the informatics system increases the registration rate and improves data entry efficiency and quality. Participants will: * Be randomly assigned to standard monitoring or informatics-assisted monitoring for irAE detection. * Have their EHR reviewed to collect demographic, medical, and cancer treatment history. * Be monitored for irAEs through daily automated analysis of their EHR data for up to 12 months or until registration in the biorepository.

In recent years, immunotherapy has become one of the important treatments for malignant tumors. Among them, PD-1 inhibitors have been widely used in clinical practice, and have shown a significant survival benefits in many patients. However, the incidence of immune-related adverse reactions (irAEs) of PD-1 inhibitors is relatively high, and severe cases can even threaten patients's life. At present, irAEs have become a bottleneck and it is urgent to establish a prevention strategy for the prediction of irAEs. In this study, the investigators intends to use Sintilimab as the research drug. A prospective cohort study was carried out. Part of the sample which was used as a training set would be detected for producing a time-series multi-dimensional data such as differential genes, metabolites and immune factors. Then gene expression programming (GEP) was used to explore the irAEs recognition model. Then, based on this recognition model, internal verification ( part of samples from the center 1 ) and external verification ( part of samples from the center 2 and center 3 samples) are carried out to accurately predict the high-risk population of irAEs and realize the early-stage warning of Sintilimab induced- irAEs.

The main goal of this prospective non-interventional exploratory monocentric study is to characterize the immune cell composition of bronchoalveolar lavage (BAL) fluid from cancer patients experiencing cancer therapy-induced pneumonitis on a single-cell scale. These mechanistic insights can directly lead to putative diagnostic biomarkers and therapeutic targets. A second highly clinically relevant hypothesis is that single-cell profiling of blood samples will reveal circulating biomarkers of ICB toxicity, making non-invasive diagnosis feasible.