Targeted immunotherapies, particularly immune checkpoint inhibitors (ICIs), have transformed cancer treatment by significantly improving patient response and survival rates. However, ICIs could disrupt self-tolerance, inducing the development of immune-related adverse events (irAEs). Most irAEs are classified as autoimmune conditions mediated by ICI-activated CD8+ cytotoxic T cells or activated B cells producing pathogenic autoantibodies. These irAEs phenotypically resemble spontaneous autoimmune disease and lead to considerable morbidity, health care costs, and compromised treatment efficacy. With the widespread use and new emergence of ICIs, the spectrum of ICI-induced irAEs has become increasingly extensive and complex. Concurrently, research in this field is advancing rapidly, a review summarizing the latest progress on irAEs is timely and essential. In this review, we highlight numerous recent research advances, covering the epidemiology, immune mechanisms, and diverse manifestations of irAEs, with a particular focus on organ-specific autoimmunity. We also discuss current strategies, challenges, and future directions for the prevention and therapeutic management of these adverse events.

The impact of incorporating immune checkpoint inhibitors (ICIs) into standard chemotherapy on the severity and risk of myelosuppression in advanced non-small cell lung cancer (NSCLC) patients remains uncertain.

We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) that evaluated ICIs in people with NSCLC. A comprehensive search of four databases, PubMed, Web of Science, Embase, and the Cochrane Library, was carried out from inception to 30 October 2023. Pooled analyses assessed the risk ratios (RR) for treatment-related hematological adverse events greater than or equal to grade 3. The protocol is registered with PROSPERO and has the CRD42024500056 registration number.

Twenty-three phase 3 RCTs were contained, involving 15,844 people with NSCLC receiving ICIs with or without chemotherapy. Compared with chemotherapy alone, ICI monotherapy or dual immunotherapy reduced treatment-associated leukopenia (relative risk (RR) 0.03, 95% CI 0.01-0.08), neutropenia (RR 0.02, 95% CI 0.01-0.03), thrombocytopenia (RR 0.05, 95% CI 0.02-0.14), and anemia (RR 0.09, 95% CI 0.05-0.15), with a pooled incidence of 0.07%, 0.08%, 0.14%, and 9.07%. Compared with chemotherapy alone, ICIs in combination with chemotherapy increased the risk of developing treatment-related thrombocytopenia (RR 1.35, 95% CI 1.04-1.77), with a pooled incidence rate of 6.83%; it did not increase leukopenia (RR 0.97, 95% CI 0.70-1.35), neutropenia (RR 1.05, 95% CI 0.90-1.23), and anemia (RR 1.10, 95% CI 0.85-1.43), with pooled incidence rates of 4.47%, 14.67%, and 13.36%, respectively.

For patients with advanced or metastatic NSCLC, severe hematological adverse events are uncommon when ICIs are used alone, as opposed to chemotherapy. However, when used in conjunction with chemotherapy, these side effects may be intensified, particularly in the form of an elevated incidence of thrombocytopenia of grade 3 or higher.

It is crucial to accurately identify patients with cancer at high risk for immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs). The present retrospective study analyzed the risk factors for irAEs in 992 patients with cancer treated with ICIs at Xi'an International Medical Center Hospital from December 2021 to December 2023. The patients were categorized into one group that experienced irAEs (n=276) and a control group (n=716) based on the occurrence of irAEs. The clinical characteristics of irAEs group (n=276) and control group (n=716) were analyzed to identify the risk factors of irAEs in patients with cancer. Multivariate regression analysis revealed significant differences between the two groups in terms of hypertension, primary cancer, metastasis, targeted drug combination and radiotherapy (P<0.05). A nomogram predictive model for irAEs was developed based on the relevant risk factors. The predictive model for irAEs in patients with cancer yielded an area under the receiver operating characteristic (ROC) curve of 0.672 (95% confidence interval: 0.630-0.714). In the validation set, the Hosmer-Lemeshow goodness-of-fit test demonstrated a favorable fit with a chi-square value of 0.787 and a P-value of 0.978. The developed predictive model can effectively identify high-risk patients with irAEs, facilitate early identification of irAEs, thereby optimizing the management strategies of irAEs, and ultimately improving the quality of life for patients.

Thyroid dysfunction is a common immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs) that target PD-1, PD-L1, and CTLA-4. Nevertheless, the incidence of severe cases, defined as grade 3 or higher, remains rare. This report presents a detailed case study of severe thyroiditis in a patient with non-small cell lung cancer (NSCLC) who developed grade 3 thyroiditis following a single cycle of sintilimab monotherapy. The clinical presentation in this patient was remarkable for its early onset, occurring one week after the initiation of sintilimab therapy, and for its severe manifestations. During hospitalization, a prompt and accurate differential diagnosis was performed. Sintilimab treatment was discontinued, and the patient was promptly started on high-dose glucocorticoids, with a tapering schedule implemented as the condition improved or reached Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or lower. The patient subsequently developed overt hypothyroidism, necessitating the initiation of thyroxine replacement therapy. Furthermore, we provide a comprehensive review of the mechanisms and risk factors associated with thyroid dysfunction immune-related adverse events (TD-irAEs). It is imperative for clinicians to meticulously monitor the clinical symptoms exhibited by patients. For those presenting with symptoms, prompt diagnosis and appropriate symptomatic management are essential. Additionally, regular thyroid function testing is recommended for high-risk patients, and we advocate for the assessment of baseline levels of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TGAb) prior to initiating ICI treatment.

Immunotherapy has changed the treatment landscape for patients with cancer in the past decade. Immune checkpoint inhibitor (ICI)-based therapies have proven effective in a range of malignancies, including liver and gastrointestinal cancers, but they can cause diverse off-target organ toxicities. With the increasingly wider application of these drugs, immune-mediated liver injury from ICIs has become a commonly encountered challenge in clinical hepatology and gastroenterology. In this Review, we discuss the evidence from human and animal studies on the immunological mechanisms of immune-mediated liver injury from ICIs and summarize its clinical features and practical considerations for its management.

Cancer treatments, although life prolonging, are associated with side effects. The occurrence, duration, and severity of side effects vary, depending on treatment received. Long-term effects refer to effects that manifest during treatment and persist long after treatment has ended. Late effects are complications that occur after treatment has ended. These effects can have a negative impact on the functioning and quality of life of persons living with and beyond cancer. This overview aims to provide a non-exhaustive overview of the long-term and late effects associated with the traditional mainstay of cancer treatments (surgery, radiotherapy, chemotherapy) and newer treatments such as immunotherapy. In conclusion, long-term and late effects of cancer treatment can be associated with a high burden for those affected, including a reduction in their ability to function and health-related quality of life. Given the large and further growing number of cancer survivors and the abundance of long-term and late effects, it is essential to develop and implement risk-adapted, multidisciplinary survivorship care programmes.

A recent study published in the World Journal of Gastroenterology, suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease (IBD), particularly Crohn's disease. In addition, that paper illustrates the effect of changes in the gut microbiota on IBD and points out that altered mesenteric adipose tissue caused by the gut microbiota and creeping fat lead to increased inflammation, which exacerbates IBD. Moreover, recent research has shown that the interaction between Helicobacter pylori (H. pylori) and the gut microbiota is mediated through immune mechanisms, resulting in a synergistic impact on IBD. Therefore, in this manuscript, we will focus on the role of the gut microbiota and H. pylori in the immune response to IBD, as well as the possible impact of H. pylori on the gut microbiota. We will also explore their individual and synergistic immune effects on IBD and look at future therapeutic perspectives for IBD.

The significance of local radiotherapy (RT) in advanced non-small-cell lung cancer (NSCLC) is well documented. However, the advent of immunotherapy has raised questions regarding the synergistic survival benefits or potential adverse effects.

This study aimed to explore whether a combination of RT and systematic immune checkpoint inhibitors (ICIs) can improve the survival outcomes for NSCLC patients.

Based on collected data patients who received RT were defined as the RT group, and those who had not for any site were defined as the non-RT group. Propensity score matching (PSM) was employed to mitigate bias. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and treatment-related adverse events (AEs).

Out of 709 patients (235 in RT group and 474 in non-RT group) were included, with 213 patients per group. The median PFS of the RT group was better than that of the non-RT group (13.8 months versus 9.5 months; p < 0.0001), although no superiority in median overall survival (OS) of the RT group was observed (p = 0.715). However, among the cohort of patients with ≤3 metastases, the median OS of the RT group improved significantly (HR = 0.60, [95% CI 0.44-0.83]; p = 0.004). Treatment-related AEs occurred in 94.5% of RT group patients and in 94.9% of non-RT group patients (p = 0.792), which indicated no observable increase in AEs from RT.

These results demonstrate the tolerability of RT when administered along with immunotherapy, suggesting its potential to positively impact the survival outcomes of NSCLC patients.

Immune checkpoint inhibitors (ICIs) significantly improve survival, while immune-mediated hepatotoxicity (IMH) has been reported. To evaluate the incidence and potential risk factors of IMH among cancer patients treated by ICIs, PubMed/Medline, Web of Science, Cochrane, and Embase were searched before 30 March 2024 for systematic review and meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Quality assessment was completed using the Newcastle-Ottawa scale. Of 1217 articles identified, 24 consisting of 9076 patients were included, with one study being prospective and the rest retrospective. The overall incidence of any grade IMH and grade ≥ 3 secondary to ICIs was 14% and 7%, respectively. The cholestatic pattern was more prevalent than the hepatocellular and mixed patterns. The meta-analysis revealed that ICI treatment was related to reduced risk of IMH in older patients (SMD: -0.18; 95% CI: -0.33 to -0.04), individuals with higher body mass index (WMD: -2.15; 95% CI: -3.92 to -0.38), males (OR: 0.44; 95% CI: 0.27 to 0.72), and patients with lung cancer (OR: 0.58, 95%CI 0.41 to 0.83). On the other hand, patients with liver metastasis (OR: 1.80; 95% CI: 1.47 to 2.20), history of ICI treatment (OR: 3.09; 95% CI: 1.21 to 7.89), diabetes (OR: 2.19; 95% CI: 1.36 to 3.51), chronic HBV (OR: 3.06; 95% CI: 1.11 to 8.46), and concomitant use of ICIs (OR: 8.73; 95% CI: 2.41 to 31.59) increased the risk of developing IMH. This study will provide clinicians with information on potentially high-risk groups for IMH, who need to be cautiously monitored for liver function when receiving immunotherapy.

Chemotherapy combined with PD-1 inhibitor treatment has revolutionized the standard of care for patients with NSCLC. However, the benefit is not universal, highlighting the need for precise prediction factors. Given their relationship with the immune system and non-invasive nature, serum cytokines are potential candidates for predicting the clinical effects of chemoimmunotherapy. Our study aims to evaluate the association of serum cytokines with the prognosis of patients with NSCLC treated with chemoimmunotherapy.

Levels of 10 serum cytokines were detected in 60 NSCLC patients receiving chemotherapy plus PD-1 inhibitor-based treatment. Of these, dynamic samples from 19 patients were collected at baseline and after two treatment cycles. Their association with patients' clinicopathological characteristics, PFS and OS was described and investigated using survival analysis, cox regression and time-dependent ROC analysis. Preliminary evaluation of changes in cytokine levels associated with treatment response was conducted.

Patients with lower baseline levels of serum IL-6, IL-5, IL-8, TNF-α and IL-10 had longer PFS, while patients with higher levels of IL-4 had longer PFS. Patients with lower levels of serum IL-6, IL-8, IL-22, TNF-α and IL-10 had longer OS, while patients with higher levels of IL-4 had longer OS. Multivariate analysis suggested that higher IL-6 and IL-5 levels were associated with poorer PFS, and higher IL-6 levels were associated with dismal OS. Additionally, changes in serum cytokine levels could be associated with treatment response.

Our study suggests that serum cytokines, specifically IL-6, IL-5, IL-8, TNF-α, IL-10, and IL-4, are potential prognostic factors for patients with NSCLC receiving chemotherapy plus PD-1 inhibitor treatment.

In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses.

This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170).

With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P < 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P < 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P = 0.036).

The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis.

National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

Chemotherapy, radiotherapy, and immunotherapy represent key tumour treatment strategies. Notably, immune checkpoint inhibitors (ICIs), particularly anti-programmed cell death 1 (PD1) and anti-programmed cell death ligand 1 (PD-L1), have shown clinical efficacy in clinical tumour immunotherapy. However, the limited effectiveness of ICIs is evident due to many cancers exhibiting poor responses to this treatment. An emerging avenue involves triggering non-apoptotic regulated cell death (RCD), a significant mechanism driving cancer cell death in diverse cancer treatments. Recent research demonstrates that combining RCD inducers with ICIs significantly enhances their antitumor efficacy across various cancer types. The use of anti-PD-1/PD-L1 immunotherapy activates CD8+ T cells, prompting the initiation of novel RCD forms, such as ferroptosis, pyroptosis, and necroptosis. However, the functions and mechanisms of non-apoptotic RCD in anti-PD1/PD-L1 therapy remain insufficiently explored. This review summarises the emerging roles of ferroptosis, pyroptosis, and necroptosis in anti-PD1/PD-L1 immunotherapy. It emphasises the synergy between nanomaterials and PD-1/PD-L1 inhibitors to induce non-apoptotic RCD in different cancer types. Furthermore, targeting cell death signalling pathways in combination with anti-PD1/PD-L1 therapies holds promise as a prospective immunotherapy strategy for tumour treatment.

This study aimed to identify the 25 most prevalent adverse events (AEs) associated with FDA-approved immune checkpoint inhibitors (ICIs)-specifically, PD-1, PD-L1, CTLA-4, and LAG-3 inhibitors-using data from the FDA Adverse Events Reporting System (FAERS), a publicly available repository of reported drug adverse events, and AERSMine, an open-access pharmacovigilance tool, to investigate these adverse events. For PD-1 inhibitors, the most common AEs were diarrhea, fatigue, and pyrexia, with notable instances of neutropenia and hypothyroidism, particularly with toripalimab and dostarlimab. PD-L1 inhibitors also frequently caused pyrexia, diarrhea, and fatigue, with interstitial lung disease and hypothyroidism showing a class effect, and drug-specific AEs such as hepatotoxicity and chills. CTLA-4 inhibitors predominantly resulted in diarrhea and colitis, with ipilimumab frequently causing pyrexia and rash, while tremelimumab exhibited unique AEs such as biliary tract infection. The LAG-3 inhibitor relatlimab reported fewer AEs, including pyrexia and pneumonia. Rare but significant AEs across all inhibitors included myocarditis and myasthenia gravis. This study provides a detailed overview of the 25 most common AEs associated with ICIs, offering valuable insights for clinical decision-making and AE management. Further research is necessary to elucidate the mechanisms underlying these AEs and to develop targeted interventions to enhance the safety and efficacy of ICI therapy in patients with cancer.

Leukemia poses a significant clinical challenge due to its swift onset, rapid progression, and treatment-related complications. Tumor immune evasion, facilitated by immune checkpoints like programmed death receptor 1/programmed death receptor ligand 1 (PD-1/PD-L1), plays a critical role in leukemia pathogenesis and progression. In this review, we summarized the research progress and therapeutic potential of PD-L1 in leukemia, focusing on targeted therapy and immunotherapy. Recent clinical trials have demonstrated promising outcomes with PD-L1 inhibitors, highlighting their role in enhancing treatment efficacy. This review discusses the implications of PD-L1 expression levels on treatment response and long-term survival rates in leukemia patients. Furthermore, we address the challenges and opportunities in immunotherapy, emphasizing the need for personalized approaches and combination therapies to optimize PD-L1 inhibition in leukemia management. Future research prospects include exploring novel treatment strategies and addressing immune-related adverse events to improve clinical outcomes in leukemia. Overall, this review provides valuable insights into the role of PD-L1 in leukemia and its potential as a therapeutic target in the evolving landscape of leukemia treatment.

Advances in oncology treatment methods have improved outcomes and quality of life for patients with cancer. However, care of these patients can be complex, and the contribution of physicians from different specialties is crucial. This article highlights important publications from 2023 on topics across a wide spectrum relating to the management of oncology patients. The literature was screened for significant new evidence that is relevant to internal medicine specialists and subspecialists whose focus is not oncology. Two articles address the importance of social interventions targeting end-of-life care for low-income and minority patients and the well-being of caregivers. Two additional articles address screening considerations in patients at risk for colorectal and lung cancer. Two more articles address safe use of hormone-related therapies to treat symptoms of menopause and prevent disease recurrence or progression in patients diagnosed with noninvasive breast neoplasia. Finally, several articles were included on topics related to COVID-19 vaccination in patients with cancer, use of cannabinoids for cancer pain control, chronic autoimmune adverse effects related to use of immune checkpoint inhibitors, and the incidence of second primary neoplasms.

The use of immune checkpoint inhibitors (ICIs) in cancer is increasing. Their side effects are mainly due to the triggering of autoimmunity, which are mild or moderate and include skin rash, colitis, hepatitis, endocrine disorders, myositis, interstitial lung disorder, etc., in most cases during the course of therapy. Autoimmune encephalitis (AE) is rare in cancer patients treated with ICIs. Fifty patients with ICI-related encephalitis were identified in a recent review. Herein, we report a case of pembrolizumab associated with AE with a favorable short-term prognosis. A 68-year-old man with malignant metastatic melanoma achieved complete remission after pembrolizumab treatment. However, 10 months after pembrolizumab cessation due to grade 3 diarrhea, he developed confusion, an altered mental status, progressive memory loss, and gait disturbance. He was admitted to the neurologic department, and a comprehensive neurological workup, brain magnetic resonance imaging, cerebral fluid analysis, EEG, and blood test allowed the diagnosis of autoimmune encephalitis. The patient was treated with plasmapheresis, a high dose of intravenous steroids, and intravenous immunoglobulins. The patient improved, and he is now well with a performance status of 1. This case is interesting since the AE developed approximately 10 months after the cessation of immunotherapy, the underlying cancer was in complete remission, and the AE showed a good response after the treatment was performed.