Immune-Related Adverse Events (irAEs): Implications for Immune Checkpoint Inhibitor Therapy

Zhou, Nanruoyi; Velez, Maria A.; Owen, Dwight H.; Lisberg, Aaron

doi:10.6004/jnccn.2020.7640

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…Immune checkpoint inhibitors have a different spectrum of toxicities when compared to chemotherapeutic or other biological agents, and the severity of irAEs appears to depend on immunotherapy regimens. For instance, in a phase III clinical trial that tested the safety and efficacy of atezolizumab and bevacizumab (anti-VEGF-A) plus carboplatin and paclitaxel (chemotherapeutic agents) in non-small lung cancer (NSCLC) resulted in pneumonitis [28][29][30]. This is also evidenced in a meta-analysis that compared the toxicity profile amongst different ICB drugs, including nivolumab, pembrolizumab, ipilimumab, tremelimumab, and atezolizumab.…”

Section: Immune-related Adverse Events Of Icb Therapymentioning

confidence: 99%

Transcriptional Regulation of Cancer Immune Checkpoints: Emerging Strategies for Immunotherapy

et al. 2020

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The study of immune evasion has gained a well-deserved eminence in cancer research by successfully developing a new class of therapeutics, immune checkpoint inhibitors, such as pembrolizumab and nivolumab, anti-PD-1 antibodies. By aiming at the immune checkpoint blockade (ICB), these new therapeutics have advanced cancer treatment with notable increases in overall survival and tumor remission. However, recent reports reveal that 40–60% of patients fail to benefit from ICB therapy due to acquired resistance or tumor relapse. This resistance may stem from increased expression of co-inhibitory immune checkpoints or alterations in the tumor microenvironment that promotes immune suppression. Because these mechanisms are poorly elucidated, the transcription factors that regulate immune checkpoints, known as “master regulators”, have garnered interest. These include AP-1, IRF-1, MYC, and STAT3, which are known to regulate PD/PD-L1 and CTLA-4. Identifying these and other potential master regulators as putative therapeutic targets or biomarkers can be facilitated by mining cancer literature, public datasets, and cancer genomics resources. In this review, we describe recent advances in master regulator identification and characterization of the mechanisms underlying immune checkpoints regulation, and discuss how these master regulators of immune checkpoint molecular expression can be targeted as a form of auxiliary therapeutic strategy to complement traditional immunotherapy.

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Section: Immune-related Adverse Events Of Icb Therapymentioning

confidence: 99%

Transcriptional Regulation of Cancer Immune Checkpoints: Emerging Strategies for Immunotherapy

et al. 2020

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“…When immune checkpoint molecules on tumor cells are aberrantly activated, the host immune system will be suppressed thereby, ICIs can subvert this established cacoethic condition, concurrently if this reversion is too intense, it is unsurprising that a hyperactivation of the immune cells will be triggered with consequent immune-related adverse events ( 50 , 51 ). Given this premise, both the histological performance of tumor and liver should be included in the morphological observation of immune-related histopathologic response.…”

Section: Histopathologic Assessment Of Specimens With Ici Therapymentioning

confidence: 99%

Pathologic assessment of hepatocellular carcinoma in the era of immunotherapy: a narrative review

Wang¹,

Qian²,

Dong³

2024

Hepatobiliary Surg Nutr

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Background and Objective: Immune checkpoint inhibitor (ICI)-based therapy has achieved impressive success in various cancer types. Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma (HCC) in recent decade. Meanwhile, numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival, respectively. In this review, we aim to summarize some pragmatic histomorphologic, immunohistochemical, and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC.Methods: We searched PubMed using the terms hepatocellular carcinoma, immunotherapy, immune checkpoint inhibitor, immune checkpoint blockade, conversion therapy, neoadjuvant therapy, adjuvant therapy, biomarker, pathologic evaluation, pathologic assessment till February 2023.

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“…Their presence prevents attacking on their own tissues due to the strengthening of the immune system. However, the corresponding receptors are also expressed on tumor cells, which prevents the immune system from killing tumor cells ( Zhou et al, 2020a ). Although immune checkpoint inhibitors disrupt the balance between immune cells and tumor cells, they also have a serious consequence: immune-related adverse events (irAEs) ( Zhou et al, 2020a ).…”

Section: Introductionmentioning

confidence: 99%

“…However, the corresponding receptors are also expressed on tumor cells, which prevents the immune system from killing tumor cells ( Zhou et al, 2020a ). Although immune checkpoint inhibitors disrupt the balance between immune cells and tumor cells, they also have a serious consequence: immune-related adverse events (irAEs) ( Zhou et al, 2020a ). IrAEs arise from inflammatory overreactions, usually involving endocrine glands, caused by immune enhancement.…”

Section: Introductionmentioning

confidence: 99%

Engineered nanomaterials trigger abscopal effect in immunotherapy of metastatic cancers

Xia

Yang

Zhu

et al. 2022

Front. Bioeng. Biotechnol.

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Despite advances in cancer treatment, metastatic cancer is still the main cause of death in cancer patients. At present, the treatment of metastatic cancer is limited to palliative care. The abscopal effect is a rare phenomenon in which shrinkage of metastatic tumors occurs simultaneously with the shrinkage of a tumor receiving localized treatment, such as local radiotherapy or immunotherapy. Immunotherapy shows promise for cancer treatment, but it also leads to consequences such as low responsiveness and immune-related adverse events. As a promising target-based approach, intravenous or intratumoral injection of nanomaterials provides new opportunities for improving cancer immunotherapy. Chemically modified nanomaterials may be able to trigger the abscopal effect by regulating immune cells. This review discusses the use of nanomaterials in killing metastatic tumor cells through the regulation of immune cells and the prospects of such nanomaterials for clinical use.

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Immune-Related Adverse Events (irAEs): Implications for Immune Checkpoint Inhibitor Therapy

Cited by 7 publications

References 32 publications

Transcriptional Regulation of Cancer Immune Checkpoints: Emerging Strategies for Immunotherapy

Transcriptional Regulation of Cancer Immune Checkpoints: Emerging Strategies for Immunotherapy

Pathologic assessment of hepatocellular carcinoma in the era of immunotherapy: a narrative review

Engineered nanomaterials trigger abscopal effect in immunotherapy of metastatic cancers

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