Background: Immune checkpoint inhibitors (ICIs) are increasingly included in management guidelines for various types of cancer. However, immune-related adverse events (irAEs) are an inevitable consequence of these therapies. Some of these side effects, such as pneumonitis, can be particularly serious. Additionally, the combination of ICIs with radiotherapy (RT) may further increase the risk of pneumonitis. Objective: The aim of this systematic review is to examine all available studies on pneumonitis following the use of ICIs and RT to assess its appearance and severity. Methods: We systematically searched four different databases (PubMed, Scopus, Cochrane, and DOAJ) to identify all relevant studies within our scope. Additionally, we reviewed the references of the studies we found, as well as those of other systematic reviews and meta-analyses. We assessed the risk of bias using the Cochrane Risk of Bias Tool version 2 for randomized controlled trials and the RTI Risk of Bias Item Bank for non-randomized trials. Finally, we extracted relevant data into an Excel file and presented them in tables throughout this study. Results: A total of 58 articles met our inclusion criteria, comprising 4889 patients across multiple studies and nine case reports. Due to significant heterogeneity in study methodologies and data reporting, a cumulative statistical analysis was not performed. The included studies were published between 2017 and 2025. The incidence of pneumonitis varied, with retrospective studies showing higher rates compared to randomized and non-randomized controlled trials. Case reports described a range of pneumonitis presentations, treatments, and outcomes, with corticosteroids being the primary treatment. Conclusions: The incidence of pneumonitis varied, with retrospective studies showing the highest rates compared to other study designs. Early detection and management of pneumonitis in patients receiving RT and/or ICIs are crucial for improving outcomes. Identifying high-risk patients through predictive models, radiomics, and biomarkers may help tailor treatment strategies and minimize toxicity. Further research is needed to establish the most appropriate diagnostic criteria, optimize management approaches, and refine advanced imaging and biomarker-based risk stratification to improve patient care. Interdisciplinary collaboration is essential for reducing the risk of pneumonitis and improving patient outcomes.

Background: Gastric cancer (GC) is one of the most common and aggressive types of cancer. Immune checkpoint inhibitors (ICIs) have proven effective in treating various types of cancer. The use of ICIs in GC patients is currently an area of ongoing research. The tumor microenvironment (TME) also seems to play a crucial role in cancer progression. Tumor-associated macrophages (TAMs) are the most abundant population in the TME. TAMs are capable of displaying programmed cell death protein 1 (PD-1) on their surface and can form a ligand with programmed death ligand 1 (PD-L1), which is found on the surface of cancer cells. Therefore, it is expected that TAMs may significantly influence the immune response related to immune checkpoint inhibitors (ICIs). Aim of the study: Understanding the role of TAMs and PD-1/PD-L1 networking in GC. Methods: A systematic review of published data was performed using MEDLINE (PubMed), Embase, and Cochrane databases. We retrieved articles investigating the co-existence of TAMs and PD-1 in GC and the prognosis of patients expressing high levels of PD-1+ TAMs. Results: Ten articles with a total of 2277 patients were included in the systematic review. The examined data suggest that the expression of PD-L1 has a positive correlation with the infiltration of TAMs and that patients who express high levels of PD-1+ TAMs may have a worse prognosis than those who express low levels of PD-1+ TAMs. Conclusions: TAMs play a pivotal role in the regulation of PD-1/PD-L1 networking and the progression of GC cells. Nevertheless, additional studies are needed to better define the role of TAMs and PD-1/PD-L1 networking in GC.

Immune-mediated necrotizing myopathy (IMNM), a type of inflammatory myopathy, is associated with anti-SRP or anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies, with statin use potentially inducing statin-associated IMNM (SAIMNM) due to HMGCR targeting. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may offer a safer alternative for lipid-lowering in these patients. This study aims to describe the clinical characteristics of SAIMNM patients and evaluate the safety of PCSK9 inhibitors after myositis onset. We present the clinical characteristics of five SAIMNM patients and evaluate the safety of PCSK9 inhibitors in these cases. Additionally, we conducted a literature review using four different databases (Medline/PubMed, Scopus, Cochrane and DOAJ) to summarize the available data on IMNM. While numerous articles discussed statin-induced myositis, we selected only those studies that addressed the treatment of dyslipidemia after the management of IMNM. All five patients were women, with four having a history of statin use. One statin-naïve patient was positive for anti-SRP antibodies, while the others had anti-HMGCR antibodies. After a mean follow-up of 18.2 months, creatine phosphokinase (CPK) levels dropped from 1028.6 IU/L to 135 IU/L, and LDL cholesterol levels decreased from 206.2 mg/dL to 87.2 mg/dL. All patients were treated with steroids (with a gradual dosage reduction), and four of the five received second line immunosuppressive therapy, such as intravenous immunoglobulin, methotrexate, azathioprine, and mycophenolate mofetil. No disease recurrence occurred after starting PCSK9 inhibitors. A review of seven studies (15 patients) showed a mean CPK of 1531.9 IU/L. 40% received steroids and another immunosuppressant. Statin rechallenge caused relapse in two cases, but PCSK9 inhibitors were well tolerated, with only one patient needing additional immunosuppression. Additionally, ezetimibe and bempedoic acid were used successfully in some patients. Finally, lipid levels appeared to be lower after treatment with PCSK9 inhibitors. Administration of PCSK9 inhibitors appears to be an effective and safe option for the treatment of dyslipidaemia in patients with IMNM.

Introduction: The introduction of immune checkpoint inhibitors (ICIs) has opened a new chapter in cancer treatment. Nevertheless, their use may result in immune-related adverse events (irAEs) with multifactorial determinants, complex mechanisms, and varying clinical implications. In specific cancer types, like melanoma, irAEs exhibit a complex relationship with patient outcomes. Case Presentation: We present a case of febrile neutropenia following ICI therapy in a patient with metastatic melanoma, underscoring the intricate clinical landscape associated with irAEs in the context of cancer immunotherapy. More specifically, a 68-year-old man was diagnosed with metastatic malignant melanoma and administered a combination of nivolumab and ipilimumab. However, after a single dose, the patient was hospitalized due to febrile neutropenia. The patient eventually recovered, but a diagnosis of myelosuppression related to prior immunotherapy led to treatment discontinuation. Subsequently, the patient transitioned to a second-line therapy. Conclusion: This case contributes to our comprehension of rare yet potentially severe hematological irAEs and their influence on immunotherapy outcomes. Such insights will guide future diagnostic and therapeutic strategies in the field of immunotherapy.

Immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 inhibitors, have become the standard of care for many cancer types. However, they induce immune-related adverse events (irAEs), including neurotoxicity and hypophysitis. The incidence and outcomes of neurotoxicity and hypophysitis in patients treated with immune checkpoint inhibitors are not well established. We conducted a retrospective study of 812 patients with solid cancers who received immune checkpoint inhibitors at the University General Hospital of Ioannina between January 2018 and January 2023. We assessed demographic and clinical data, including the severity of symptoms, treatment regimen, other irAEs, resolution type and time, and death. Two patients experienced neurotoxicity and two hypophysitis. All four patients required inpatient administration and received corticosteroids or/and hormone replacement. Three patients responded to the initial therapy, experiencing full recovery, while one patient was corticosteroid-resistant, and immunoglobin G was administered. Two patients never received immunotherapy after their toxicity due to the severity of symptoms; one patient continued monotherapy with nivolumab, changing from combination therapy with ipilimumab–nivolumab, while the fourth patient continued his initial treatment with nivolumab. Our study suggests that the incidence of neurotoxicity and hypophysitis in patients treated with immune checkpoint inhibitors is low, but careful monitoring and prompt treatment with corticosteroids are necessary for effective management.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by enhancing the immune response against tumors. However, they can cause immune-related adverse events (irAEs), including rare but potentially fatal myocarditis. We describe a 71-year-old man with stage IIIA lung adenocarcinoma treated with adjuvant pembrolizumab who developed severe ICI-associated myocarditis. Despite early diagnosis, treatment with intensive immunosuppression and mechanical support, he suffered fatal cardiac complications. A systematic review of the literature up to May 2025 identified 44 cases of ICI-associated myocarditis. Data on clinical features, diagnostics, treatment, and outcomes were extracted and analyzed. Most cases involved older patients with lung cancer treated with pembrolizumab or nivolumab. Onset varied from days to years after therapy initiation. Presentations included dyspnea, chest pain, arrhythmias, and elevated cardiac biomarkers. The biopsy showed T-cell and macrophage infiltration. High-dose corticosteroids were the primary treatment; additional immunosuppressants were used in cases that were refractory. Mortality was 45%, mainly due to cardiac failure and sepsis. Discussion: ICI-associated myocarditis arises from immune dysregulation affecting cardiac tissue, potentially involving shared antigens and systemic inflammation. Early detection and aggressive immunosuppression are crucial but often insufficient, resulting in high mortality. This underscores the urgent need for a better understanding of pathogenesis and the development of effective management strategies to improve patient outcomes. Finally, a multidisciplinary approach is important to improve outcomes in ICI-associated myocarditis.