Immune Agents Research Articles

Emerging innovative treatment strategies for advanced clear cell renal cell carcinoma.

Dramatic advances in biological discoveries, since the 1990s, have continued to reshape the treatment paradigm of metastatic renal cell carcinoma (RCC). Von Hippel Lindau (VHL) gene alterations are associated with pro-angiogenic activity and are central to the pathogenesis of clear cell RCC (ccRCC), the most predominant histologic subtype of RCC. Antiangiogenic strategies revolving around this VHL/HIF/VEGF axis have been shown to improve survival in metastatic ccRCC. The discovery of immune checkpoints and agents that target their inhibition introduced a new treatment paradigm for patients with RCC. While initially approved as monotherapy, studies investigating immune checkpoint inhibitor combinations have led to their approval as the new standard of care, providing durable responses and unprecedented improvements in clinical outcome. Despite these advances, the projected 14390 deaths in 2024 from RCC underscore the need to continue efforts in expanding and optimizing treatment options for patients with metastatic RCC. This article reviews key findings that have transformed the way we understand and treat metastatic RCC, in addition to highlighting novel treatment strategies that are currently under development.

Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies

Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%. Outcomes may vary according to stage at time of diagnosis and histologic subtype. Most recently, clinical trials utilizing dual checkpoint inhibitor regimens and chemotherapy in combination with immune oncologic agents have demonstrated impactful changes in outcomes. In this article, we review studies that have led to the successful implementation of immunotherapy in clinical practice for the treatment of this disease and highlight ongoing clinical trials exploring the use of different immunotherapy strategies for the treatment of pleural mesothelioma. We also discuss the challenges of immunotherapy-based approaches in the context of mesothelioma and future strategies currently being investigated to overcome them.

Use pembrolizumab may cause acute and severe adverse reactions: a case report and review

Introduction: Immune checkpoint inhibitors (ICIs) have emerged as pivotal therapeutics for personalized cancer treatment. Programmed death protein receptor 1/ligand 1 (PD-1/PD-L1) inhibitors represent the most extensively utilized immune checkpoint blockade agents. Among these, pembrolizumab has gained approval for advanced cancer management. By engaging with PD-1 on T cells, pembrolizumab orchestrates the immune response against tumor cells; however, it is also associated with a spectrum of adverse events, including an infrequent manifestation of fulminant type 1 diabetes. Case presentation: ICIs-induced fulminant type 1 diabetes mellitus (FT1DM) in breast cancer patients has been rarely documented. To provide further evidence of such adverse events, this paper presents the case of a 58-year-old Chinese patient with breast cancer and multi-organ metastasis, who had no prior history of diabetes. Following five courses of pembrolizumab, she developed severe fulminant type 1 diabetes accompanied by ketoacidosis. Discussion: Pembrolizumab is commonly utilized in the treatment of patients with advanced cancer. While it offers significant benefits to patients, it can also lead to numerous adverse reactions, with immune-related diabetes being the most prevalent among them as a result of pembrolizumab usage. Conclusions: FT1DM complicated with ketoacidosis represents a critical and potentially life-threatening medical condition, necessitating immediate attention. Our case study underscores the inherent risks associated with pembrolizumab administration and offers valuable insights for its safe utilization in patients.

Optimized Fabrication of Dendritic Mesoporous Silica Nanoparticles as Efficient Delivery System for Cancer Immunotherapy.

In the past decade, cancer immunotherapy has revolutionized the field of oncology. Major immunotherapy approaches such as immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, cytokines, and immunomodulators have shown great promise in preclinical and clinical settings. Among them, immunomodulatory agents including cancer vaccines are particularly appealing; however, they face limitations, notably the absence of efficient and precise targeted delivery of immune-modulatory agents to specific immune cells and the potential for off-target toxicity. Nanomaterials can play a pivotal role in addressing targeting and other challenges in cancer immunotherapy. Dendritic mesoporous silica nanoparticles (DMSNs) can enhance the efficacy of cancer vaccines by enhancing the effective loading of immune modulatory agents owing to their tunable pore sizes. In this work, an emulsion-based method is optimized to customize the pore size of DMSNs and loaded DMSNs with ovalbumin (OVA) and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (CpG-OVA-DMSNs). The immunotherapeutic effect of DMSNs is achieved through controlled chemical release of OVA and CpG in antigen-presenting cells (APCs). The results demonstrated that CpG-OVA-DMSNs efficiently activated the immune response in APCs and reduced tumor growth in the murine B16-OVA tumor model.

The Role of SIRT1 in Leukemia.

Leukemia is a type of hematological malignancy (HM) caused by uncontrolled proliferation, apoptosis, and differentiation of hematopoietic stem cells (HSCs). Leukemia cells proliferate greatly in the bone marrow (BM), infiltrate other tissues and organs, and affect the normal hematopoietic function. Although the emergence of new targeted agents and immune agents has improved the prognosis of patients, due to the complex pathogenic factors and heterogeneity of leukemia, there are still some patients with poor prognosis. Recent studies have shown that silent information regulator 1 (SIRT1) is involved in the proliferation, apoptosis, metabolism, and senescence of leukemia cells. As a double-edged sword in leukemia cells, SIRT1 can both promote and inhibit the growth of leukemia cells. Since its mechanism of action has not been elucidated, it is urgent to explore the regulatory mechanism of SIRT1 in leukemia. In this review, we discussed the mechanisms of SIRT1 in different aspects of leukemia, providing a theoretical basis for the treatment of patients with leukemia.

Pancreatic cancer is feeling the heat.

Pancreatic adenocarcinoma (PDAC) is considered an immunologically 'cold' tumor that fails to attract or support effector T cells. Most PDACs are resistant to immune checkpoint blockade due to the complex signaling pathways that exist within its tumor microenvironment. Recent advances in genomic and proteomic technology advances are finally uncovering the complex inflammatory cellular and intercellular signals that require modulation and reprogramming. The goal is to 'turn up the heat' on PDACs with combination immunotherapies that incorporate T cell activating agents and immune modulatory agents, and successfully eradicate tumors. Here, we discuss progress and promising new research that is moving the field toward this goal.

Inhibition of the Rho/MRTF pathway improves the response of BRAF-resistant melanoma to PD1/PDL1 blockade.

Metastatic cutaneous melanoma is a fatal skin cancer. Resistance to targeted and immune therapies limits the benefits of current treatments. Identifying and adding anti-resistance agents to current treatment protocols can potentially improve clinical responses. Myocardin-related transcription factor (MRTF) is a transcriptional coactivator whose activity is indirectly regulated by actin and the Rho family of GTPases. We previously demonstrated that development of BRAF inhibitor (BRAFi) resistance frequently activates the Rho/MRTF pathway in human and mouse BRAFV600E melanomas. In clinical trials, pretreatment with BRAFi reduces the benefit of immune therapies. We aimed to test the efficacy of concurrent treatment with our MRTF pathway inhibitor CCG-257081 and anti-PD1 in vivo and to examine its effects on the melanoma immune microenvironment. Because MRTF pathway activation upregulates the expression of immune checkpoint inhibitor genes/proteins, we asked whether CCG-257081 can improve the response to immune checkpoint blockade. CCG-257081 reduced the expression of PDL1 in BRAFi-resistant melanoma cells and decreased surface PDL1 levels on both BRAFi-sensitive and -resistant melanoma cells. Using our recently described murine vemurafenib-resistant melanoma model, we found that CCG-257081, in combination with anti-PD1 immune therapy, reduced tumor growth and increased survival. Moreover, anti-PD1/CCG-257081 co-treatment increased infiltration of CD8+ T cells and B cells into the tumor microenvironment and reduced tumor-associated macrophages. Here, we propose CCG-257081 as an anti-resistance and immune therapy-enhancing anti-melanoma agent.

Cancer bronchique à petites cellules de stade étendu : quoi de neuf ?

This article describes recent advances in the therapeutic management of extensive-stage small cell lung cancer, particularly the development of immune checkpoint inhibitors and new agents targeting DLL3. He also cites still debatable issues such as thoracic radiotherapy and prophylactic cerebral irradiation. Finally, therapeutic approaches targeting DNA damage repair abnormalities are discussed.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Toxicity of Cancer Immunotherapies in Older Patients: Does Age Make a Difference?

The use of immunotherapy agents especially immune checkpoint inhibitors is growing, and toxicities known as immune-related adverse events affecting any organ system may develop as a consequence of the treatment. With an ageing population, a considerable number of patients who will receive these therapies will be older adults. However, older patients who have highly heterogenous clinical characteristics, age-related changes in the immune system, a higher prevalence of comorbidities and frailty have been poorly represented in clinical trials, leaving gaps in understanding the safety of immune checkpoint inhibitor agents in this subgroup. Therefore, the safety of immune checkpoint inhibitors is a primary point of consideration when treating older patients with cancer. The available evidence is conflicting, but it generally suggests that the incidence of immune-related adverse events is not necessarily higher in older patients, but it may have a different profile. It is important to also note that the management of immune-related adverse events can be a challenge in these patients, owing to the risks associated with the use of corticosteroids and a reduced physiological reserve. A comprehensive characterisation of immune ageing, potential biomarkers to predict immune-related adverse events, the use of measures for frailty, enrolling older patients with cancer to clinical trials and analysis of real-world data are necessary to improve the evidence-based decision making for immune checkpoint inhibitor treatment in a geriatric oncology population.

Regional diversity in drug-induced lung diseases among the USA, European Union, and Japan.

Drug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base. This retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and cytotoxic agents. Regional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418). The prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.

Digital oncology, the dawn of a new era turning the clock back on tumor mass

Evolutionary path of cancer therapeutics which started around eighty-two years ago, following serendipitous discovery of nitrogen mustard [1] has been guided by an accelerated pace of new discoveries, an ever-increasing depth of understanding of intracellular biological processes [2] and application of advances made in other fields of science [3]. Success in any field, especially in cancer medicine, is based on embracing evolution in understanding other scientific fields [4] and its application to the forward move in cancer therapeutics. As such, we have gone through discovery of a diverse group of therapeutics, targeting different sub compartments of growth and proliferation pathways [5] and taking advantage of their synergistic efficacy, in different combinations [6]. Dissection of immune regulatory pathways [7] and their interaction with cancer cell has led to the generation of modern immune therapeutic agents. Single-cell sequencing technology [8] has paved the way for the development of spatial omics [9], which has opened the way on deeper understanding of tumor evolutionary path [10]. This would give us the opportunity to design a new generation of cancer therapeutics [11] intercepting with the forward evolutionary path of tumor mass. Along this path, we face insurmountable barriers in developing meaningful and game changing treatment strategies by directing single changes in a hyper complex biological system [12], manifested by complexities of genome [13], epigenome [14], microRNA network [15], gene regulatory mechanisms [16], and protein-protein interactions [17]. Consequently, we need to search for a solution that enables us to freeze or slow down the forward evolutionary path of tumor mass [18], by making a single change in a game changing variable of cancer cell.

PROBLEMS OF MANAGING THE IMMUNE RESPONSE UNDER CONDITIONS OF COMPETITIVE ADSORPTION, DIFFUSION PERTURBATIONS AND TEMPERATURE RESPONSE OF THE ORGANISM

Analysis of the problems associated with the rapid spread of infectious diseases indicates the need for new approaches to the diagnosis and develop- ment of effective personalized treatment programs. One of the important aspects of solving this problem is the creation of a mathematical modeling toolkit for predicting the dynamics of infectious diseases, taking into account spatial effects, concentrated effects, various mechanisms of body protec- tion in the conditions of the application of various types of therapeutic methods of treatment. An important component of complex methods of treat- ment of a wide range of infectious diseases is the use of adsorption drugs, which, along with detoxification of the body, are able to provide an addi- tional mechanism of neutralization of viral elements. In the process of using such means, not only pathogenic elements and toxins will be adsorbed, but also various types of immune agents, which will affect the dynamics of the immune response. In the paper the infectious disease model is generalized to take into account the features of competitive adsorption of antigens and immune agents in the conditions of diffusion perturbations, concentrated influences and temperature reaction of the body. By synthesizing the ideas of step-by-step procedures, asymptotic and numerical methods, an effective computational technology of step-by-step approximation of the solution of the original model singularly perturbed problem was built. The results of the computer experiments presented in the paper illustrate the features of reducing the predicted concentration of viral elements during their competi- tive adsorption together with immune agents, in particular, the effect of reducing the efficiency of the use of non-specific adsorbents. It is emphasized that taking into account the features of the action of competitive adsorption is important for making decisions regarding the formation of rational treatment programs with the complex use of adsorbing substances and immunological drugs.

Synthesis and Structural Characterization of a Non-Heme Iron Hyponitrite Complex.

Flavodiiron NO reductases (FNORs) are important enzymes in microbial pathogenesis, as they equip microbes with resistance to the human immune defense agent nitric oxide (NO). Despite much efforts, intermediates that would provide insight into how the non-heme diiron active sites of FNORs reduce NO to N2O could not be identified. Computations predict that iron-hyponitrite complexes are the key species, leading from NO to N2O. However, the coordination chemistry of non-heme iron centers with hyponitrite is largely unknown. In this study, we report the reactivity of two non-heme iron complexes with preformed hyponitrite. In the case of [Fe(TPA)(CH3CN)2](OTf)2, cleavage of hyponitrite and formation of an Fe2(NO)2 diamond core is observed. With less Lewis-acidic [Fe2(BMPA-PhO)2(OTf)2] (2), reaction with Na2N2O2 in polar aprotic solvent leads to the formation of a red complex, 3. X-ray crystallography shows that 3 is a tetranuclear iron-hyponitrite complex, [{Fe2(BMPA-PhO)2}2(μ-N2O2)](OTf)2, with a unique hyponitrite binding mode. This species provided the unique opportunity to us to study the interaction of hyponitrite with non-heme iron centers and the reactivity of the bound hyponitrite ligand. Here, either protonation or oxidation of 3 is found to induce N2O formation, supporting the hypothesis that hyponitrite is a viable intermediate in NO reduction.

Synthesis and Structural Characterization of a Non‐Heme Iron Hyponitrite Complex

Flavodiiron NO reductases (FNORs) are important enzymes in microbial pathogenesis, as they equip microbes with resistance to the human immune defense agent nitric oxide (NO). Despite much efforts, intermediates that would provide insight into how the non‐heme diiron active sites of FNORs reduce NO to N2O could not be identified. Computations predict that iron‐hyponitrite complexes are the key species, leading from NO to N2O. However, the coordination chemistry of non‐heme iron centers with hyponitrite is largely unknown. In this study, we report the reactivity of two non‐heme iron complexes with preformed hyponitrite. In the case of [Fe(TPA)(CH3CN)2](OTf)2, cleavage of hyponitrite and formation of an Fe2(NO)2 diamond core is observed. With less Lewis‐acidic [Fe2(BMPA‐PhO)2(OTf)2] (2), reaction with Na2N2O2 in polar aprotic solvent leads to the formation of a red complex, 3. X‐ray crystallography shows that 3 is a tetranuclear iron‐hyponitrite complex, [{Fe2(BMPA‐PhO)2}2(μ‐N2O2)](OTf)2, with a unique hyponitrite binding mode. This species provided the unique opportunity to us to study the interaction of hyponitrite with non‐heme iron centers and the reactivity of the bound hyponitrite ligand. Here, either protonation or oxidation of 3 is found to induce N2O formation, supporting the hypothesis that hyponitrite is a viable intermediate in NO reduction.

Overview of secondary immunodeficiency.

In contrast to inborn errors of immunity (IEI), which are inherited disorders of the immune system that predispose to infections, malignancy, atopy, and immune dysregulation, secondary immunodeficiencies and immune dysregulation states (SID) are acquired impairments in immune cell function and/or regulation, and may be transient, reversible, or permanent. SIDs can derive from a variety of medical comorbidities, including protein-losing conditions, malnutrition, malignancy, certain genetic syndromes, prematurity, and chronic infections. Medications, including immunosuppressive and chemotherapeutic drugs, can have profound effects on immunity and biologic agents used in rheumatology, neurology, and hematology/oncology practice are increasingly common causes of SID. Iatrogenic factors, including surgical procedures (thymectomy, splenectomy) can also contribute to SID. A thorough case history, medication review, and laboratory evaluation are necessary to identify the primary driver and determine proper management of SID. Careful consideration should be given to whether a primary IEI could be contributing to autoimmunity, malignancy, and posttreatment complications (e.g., antibody deficiency). SID management consists of addressing the driving condition and/or removing the offending agent if feasible. If SID is suspected to be permanent, then antibiotic prophylaxis, additional immunization, and immunoglobulin replacement should be considered.

Differential expression in potential therapeutic target protein by treatment in small cell lung cancer with and without transformation.

202 Background: Small cell lung cancer (SCLC) is a disease with a poor prognosis. Besides combination strategy with immune checkpoint inhibitors (ICIs) and cytotoxic agents, antibody-drug conjugates (ADCs) and bispecific T-cell engagers (BiTE) are being developed. These drugs target tumor-associated surface protein. Whether prior treatment affect the transition of protein expression has not been fully investigated especially in the era of ICIs. The purpose of this study is to evaluate changes in protein expression in SCLC tissues before and after treatment. Methods: We included patients diagnosed with SCLC by surgery or biopsy and underwent re-biopsy after treatment (non-transformed group) at the National Cancer Center Hospital between 2014 and 2023. Patients who were initially diagnosed with non-small cell lung cancer and underwent transformation to SCLC (transformed group) were also included. Tissues were obtained by surgery, bronchoscopy, or CT-guided biopsy with an interval of at least 100 days. We investigated clinicopathological features in paired specimens focusing on DLL3, ASCL1, NEUROD1, POU2F3, and YAP1, which have been reported to be expressed in SCLC, as well as tumor-associated surface proteins potentially related to novel drug development. Results: Fourteen non-transformed group cases and 9 transformed group cases were included. Of these, pathology specimens were evaluable in a total of 15 cases: 9 for the non-transformed group and 6 for the transformed group. The median age was 68 years, 11 (73%) were male, 11 (73%) were smokers, 8 (53%) were in clinical stages I-IIIA, 1 (7%) in stages IIIB and 6 (40%) in stage IV. Among the transformed group, 4 of them were treated by Osimertinib before transformation. Progression free survival from first-line therapy was 298 days (255-446) vs. 314 days (245-NA) and overall survival was 1239 days (567-NA) vs. NA days (517-NA), respectively for non-transformed group and transformed group. For both these group of cases, we have evaluated several protein expressions as described above. The transition of these proteins within each group is presented in the conference. Conclusions: In this study, we focused not only on proteins already reported to be expressed in SCLC, but also on proteins that are potential new therapeutic targets and evaluated changes in protein expression. [Table: see text]

Unravelling the Complexities and Recent Advances in the Management of Atopic Dermatitis

Abstract: Atopic dermatitis (AD) is a non-fatal, non-communicable, chronic skin inflammatory condition marked by itching, lesions, and skin barrier dysfunction. As per the International Eczema Council, as of 2022, more than 200 million people were suffering from AD, with the disease burden reported highest in children. Environmental factors, genetic predisposition, and lifestyle have been found to be essential factors in triggering the adverse skin response. In this review, we provide a detailed overview of the pathophysiology of AD, how the skin barrier gets altered from normal condition to AD, and the role of genetic defects in Filaggrin protein, affecting the skin barrier function by altering the skin pH and hydration. Also, we highlight the role of toll-like receptors (TLRs) and the altered skin and gut microbiota in inducing chronic inflammatory responses and playing a significant role in the pathogenesis of the disease. Further, we discuss the role of several chemokines and cytokines, which could serve as important prognosis markers for early detection, monitoring the disease progression, and assessing the response to the treatment. We also report the current treatment regime of multimodal therapeutics ranging from topical emollients to topical, oral, and injectable immune modulatory agents. Besides, we discuss the importance of the gut-skin microbiome axis and the increasingly important role of prebiotics in AD treatment.

Prolonged exposure to the synthetic glucocorticoid dexamethasone induces brain damage via oxidative stress and apoptotic response in adult Daniorerio

Due to its extensive use as a painkiller, anti-inflammatory, and immune modulatory agent, as well as its effectiveness in treating severe COVID-19, dexamethasone, a synthetic glucocorticoid, has gained attention not only for its impact on public health but also for its environmental implications. Various studies have reported its presence in aquatic environments, including urban waters, surface samples, sediments, drinking water, and wastewater effluents. However, limited information is available regarding its toxic effects on nontarget aquatic organisms. Therefore, this study aimed to investigate the mechanism of toxicity underlying dexamethasone-induced brain damage in the bioindicator Danio rerio following long-term exposure. Adult zebrafish were treated with environmentally relevant concentrations of dexamethasone (20, 40, and 60 ng L-1) for 28 days. To elucidate the possible mechanisms involved in the toxicity of the pharmaceutical compound, we conducted a behavioral test battery (Novel Tank and Light and Dark tests), oxidative stress biomarkers, acetylcholinesterase enzyme activity quantification, histopathological analysis, and gene expression analysis using qRT-PCR (p53, bcl-2, bax, caspase-3, nrf1, and nrf2).The results revealed that the pharmaceutical compound could produce anxiety-like symptoms, increase the oxidative-induced stress response, decrease the activity of acetylcholinesterase enzyme, and cause histopathological alterations, including perineuronal vacuolization, granular and molecular layers deterioration, cell swallowing and intracellular spaces. The expression of genes involved in the apoptotic process (p53, bax, and casp-3) and antioxidant defense (nrf1 and nrf2) was upregulated in response to oxidative damage, while the expression of the anti-apoptotic gene bcl-2 was down-regulated indicating that the environmental presence of dexamethasone may pose a threat to wildlife and human health.

Immunotherapy in Neuroendocrine Neoplasms: A Diamond to Cut.

A raise in the incidence of NENs is expected. Therefore, the identification of new therapeutic strategies, such as immunotherapy, remains crucial. To date, immune checkpoint inhibitors as monotherapy have shown modest activity in unselected NENs. Although immunotherapy combos (plus another immune agents or chemotherapy, among others) are potentially more active than single agents, this has not been uniformly confirmed, even in high-grade NENs. Other immunotherapeutic strategies under development include bispecific antibodies, targeting specific tumor antigens like DLL3, and cell therapy. Currently, no predictive immune biomarkers are available to guide clinical decisions. A comprehensive tumor molecular profiling approach needs to be developed for the selection of patients with NEN who could potentially benefit from immunotherapy. Ideally, clinical trials should incorporate this tumor molecular profiling to identify predictive biomarkers and improve efficacy. Achieving this goal requires an international collaborative effort.

Pituitary-adrenal axis dysfunction induced by tislelizumab immunotherapy for non-small cell lung cancer: a case series and literature review

BackgroundAdverse events of secondary adrenal insufficiency caused by anti-PD-1 immune agents are relatively rare in clinical practice, so in this article, we retrospectively analyzed three patients who suffered secondary adrenal cortex dysfunction caused by tislelizumab immunotherapy for Non-Small Cell Lung Cancer (NSCLC)and reviewed the literature. This rare immune-related adverse event was investigated by summarizing the clinical features of the patients.Case presentationWe reported three NSCLC patients who suffered secondary adrenal cortex dysfunction induced by tislelizumab immunotherapy at our hospital from July 2021 to October 2023. We analyzed and summarized the clinical characteristic, laboratory examination, pathological staging, etc. We also reviewed related literature of pituitary inflammation and adrenal cortex dysfunction caused by immunotherapy.ResultsThe median age of the three patients was 56 years. All the patients had a history of smoking. After receiving tislelizumab treatment (median cycle: 7), laboratory examination showed a decrease in morning cortisol and adrenocorticotropic hormone (ACTH), both were diagnosed with secondary adrenal insufficiency. Only one patient had symptoms of fatigue, vomiting, and weight loss. One of these patients also had simultaneous subclinical hypothyroidism. All three patients discontinued immunotherapy and received replacement therapy with glucocorticoids. At the last follow-up, none of the three patients restarted immunotherapy, because cortisol did not return to normal. This is similar to that of previous reports.ConclusionBased on previous reports and our three cases, when laboratory tests of NSCLC patients receiving immunotherapy showed a decrease in morning cortisol and ACTH levels, especially when clinical symptoms were obvious, the possibility of immunotherapy-related pituitary inflammation causing secondary adrenal cortex dysfunction should be considered. Prompt monitoring and hormone replacement therapy should be provided to prevent adrenal crises.