Significance of Pre-treatment Interferon-gamma Release in Patients With Non-small-cell Lung Cancer Receiving Immune Checkpoint Inhibitors

Hirashima, Tomonori; Kanai, Tomohiro; Suzuki, Hidekazu; Yoshida, Hiroko; Matsusita, Akane; Kawasumi, Hiromi; Nasu, Shingo; Tanaka, Ayako; Morishita, Naoko; Kawahara, Katsunobu; Tamura, Yoshitaka; Okamoto, Norio

doi:10.21873/anticanres.14721

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…The prediction and management of irAEs are important in clinical practice. Biomarkers for early prediction of irAEs have been explored [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. In case of non-organ specific biomarkers in CCB therapy, Das et al reported that among patients with melanoma who received CCB therapy, the proportion of B cells in the peripheral blood decreases, whereas that of CD21 lo B cells increases, after treatment in patients who developed grade 3 or higher irAEs.…”

Section: Introductionmentioning

confidence: 99%

CD21lo B Cells Could Be a Potential Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma

Nishimura

Konishi

Ochi

et al. 2022

JPM

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Immune checkpoint inhibitor (ICI) therapy increases the risk of immune-related adverse events (irAEs). In particular, combination checkpoint blockade (CCB) targeting inhibitory CTLA-4 and PD-1 receptors could lead to irAEs at a higher rate than ICI monotherapy. Management of irAEs is important while using ICIs. However, there are no reliable biomarkers for predicting irAEs. The aim of this study was to elucidate early B cell changes after CCB therapy in patients with renal cell carcinoma (RCC) and verify whether B cells can be a predictor of irAEs. This prospective cohort study was conducted with 23 Japanese patients with metastatic RCC. An increase in the proportion of CD21lo B cells and CD21lo memory B cells was confirmed following CCB therapy. Although there were no differences in clinical outcomes between irAE and no-irAE groups, the proportion of CD21lo B cells at baseline was lower in the irAE group, with a significant increase after the first cycle of CCB therapy. Further analysis revealed a moderate correlation between irAEs and CD21lo B cell levels at baseline (area under the curve: 0.83, cut-off: 3.13%, sensitivity: 92.3, specificity: 70.0). This finding indicates that patients with low baseline CD21lo B cell levels warrant closer monitoring for irAEs. The clinical registration number by the Certified Review Board of Ehime University is No. 1902011.

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Section: Introductionmentioning

confidence: 99%

CD21lo B Cells Could Be a Potential Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma

Nishimura

Konishi

Ochi

et al. 2022

JPM

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“…This task can be conducted by traditional epidemiological methods, such as cross-sectional, cohort, or case-control studies ( 147 – 149 ). The probable biomarkers that have currently been identified are either general characteristics (e.g., age ( 150 , 151 ), gender ( 152 ), and BMI ( 153 )) or common serum molecules based on the current understanding of the immunological mechanisms of cirAEs (e.g., CRP ( 154 ), IFN-γ ( 155 )). Regarding to the antigenicity, tumor mutation burden (TMB) ( 156 – 158 ) and microsatellite instability (MSI) ( 159 , 160 ), which stand for the neoantigen or onco-antigen, are used to predict the efficacy of ICIs and the risk of irAEs.…”

Section: Prediction Of Ciraesmentioning

confidence: 99%

Cutaneous immune-related adverse events to immune checkpoint inhibitors: from underlying immunological mechanisms to multi-omics prediction

Cao

Zhou

et al. 2023

Front. Immunol.

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The development of immune checkpoint inhibitors (ICIs) has dramatically altered the landscape of therapy for multiple malignancies, including urothelial carcinoma, non-small cell lung cancer, melanoma and gastric cancer. As part of their anti-tumor properties, ICIs can enhance susceptibility to inflammatory side effects known as immune-related adverse events (irAEs), in which the skin is one of the most commonly and rapidly affected organs. Although numerous questions still remain unanswered, multi-omics technologies have shed light into immunological mechanisms, as well as the correlation between ICI-induced activation of immune systems and the incidence of cirAE (cutaneous irAEs). Therefore, we reviewed integrated biological layers of omics studies combined with clinical data for the prediction biomarkers of cirAEs based on skin pathogenesis. Here, we provide an overview of a spectrum of dermatological irAEs, discuss the pathogenesis of this “off-tumor toxicity” during ICI treatment, and summarize recently investigated biomarkers that may have predictive value for cirAEs via multi-omics approach. Finally, we demonstrate the prognostic significance of cirAEs for immune checkpoint blockades.

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“…In the cellular immunity of Mycobacterium tuberculosis, the PD-1/PD-L1 axis and interferon-γ (IFN-γ) play an important role. 62 Hirashima et al 56 speculated that the release of IFN-γ in T lymphocytes would change after ICI treatment. They used QuantiFERON®-TB Gold Plus (QFT-Plus) to measure IFN-γ levels at four time points in 29 patients with NSCLC treated with ICIs and found that severe irAEs were prone to occur when IFN-γ levels were <10 IU/ml at 227 days or 437 days after ICI treatment.…”

Section: Nonorgan-specific Biomarkers Of Iraesmentioning

confidence: 99%

Biomarkers and risk factors for the early prediction of immune-related adverse events: a review

Zhang

et al. 2022

Human Vaccines & Immunotherapeutics

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In recent years, immunotherapy has been widely used to treat patients with malignant tumors. While immune checkpoint inhibitors (ICIs) significantly improve the prognosis of cancer patients, the incidence of immune-related adverse events (irAEs) is increasing. Not only can irAEs accumulate in multiple organ systems throughout the body, but rare adverse reactions may also occur continuously. In severe cases, irAEs can be life-threatening or even lead to death. Therefore, the early identification, diagnosis and treatment of irAEs are very important. Early identification of patients with high-risk irAEs as well as the reduction or avoidance of severe irAEs have important clinical significance. This article will review the research progress of early predictive biomarkers and risk factors for the occurrence of irAEs and propose potential future directions for follow-up research and clinical applications.

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Significance of Pre-treatment Interferon-gamma Release in Patients With Non-small-cell Lung Cancer Receiving Immune Checkpoint Inhibitors

Cited by 4 publications

References 17 publications

CD21lo B Cells Could Be a Potential Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma

CD21lo B Cells Could Be a Potential Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma

Cutaneous immune-related adverse events to immune checkpoint inhibitors: from underlying immunological mechanisms to multi-omics prediction

Biomarkers and risk factors for the early prediction of immune-related adverse events: a review

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