Prediction, prevention, and precision treatment of immune checkpoint inhibitor neurological toxicity using autoantibodies, cytokines, and microbiota DOI Creative Commons
Alberto Vogrig,

Marta Dentoni,

Irene Florean

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 13, 2025

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized oncology, significantly improving survival across multiple cancer types. ICIs, such as anti-PD-1 (e.g. nivolumab, pembrolizumab), anti-PD-L1 atezolizumab, avelumab), and anti-CTLA-4 ipilimumab), enhance T cell-mediated anti-tumor responses but can also trigger immune-related adverse events (irAEs). Neurological irAEs (n-irAEs), affecting 1-3% of patients, predominantly involve the peripheral nervous system; less commonly, n-irAEs present central system disorders. Although suggest a possible correlation treatment efficacy, their mechanisms remain unclear, hypotheses ranging from antigen mimicry to cytokine dysregulation microbiome alterations. Identifying patients at risk for predicting outcome through biomarkers would be highly desirable. For example, high-risk onconeural antibodies (such anti-Hu or Ma2), elevated neurofilament light chain (NfL) levels often respond poorly irAE treatment. However, interpreting neuronal antibody tests in diagnosis requires caution: positive results must align clinical context, some (e.g., SCLC) may have asymptomatic low levels, false are common without tissue-based confirmation. Also, use IL-6) lead more targeted treatments irAEs, minimizing effects compromising efficacy ICIs. This review provides comprehensive overview latest findings on associated focus prediction, prevention, well precision using autoantibodies, cytokines, microbiota. The most interesting data concern antibodies, which we explore pathogenic roles neurotoxicity. Most available both regarding role diagnostic prognostic supporting therapeutic decisions toxicities, refer non-neurological toxicities. our review, mention potential CXCL10 CXCL13 describe current evidence, need further studies, cytokines guiding selection second-line therapies n-irAEs. Finally, no specific microbiome-related microbial signature been proven linked specifically, leading future research topic.

Language: Английский

Prediction, prevention, and precision treatment of immune checkpoint inhibitor neurological toxicity using autoantibodies, cytokines, and microbiota DOI Creative Commons
Alberto Vogrig,

Marta Dentoni,

Irene Florean

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 13, 2025

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized oncology, significantly improving survival across multiple cancer types. ICIs, such as anti-PD-1 (e.g. nivolumab, pembrolizumab), anti-PD-L1 atezolizumab, avelumab), and anti-CTLA-4 ipilimumab), enhance T cell-mediated anti-tumor responses but can also trigger immune-related adverse events (irAEs). Neurological irAEs (n-irAEs), affecting 1-3% of patients, predominantly involve the peripheral nervous system; less commonly, n-irAEs present central system disorders. Although suggest a possible correlation treatment efficacy, their mechanisms remain unclear, hypotheses ranging from antigen mimicry to cytokine dysregulation microbiome alterations. Identifying patients at risk for predicting outcome through biomarkers would be highly desirable. For example, high-risk onconeural antibodies (such anti-Hu or Ma2), elevated neurofilament light chain (NfL) levels often respond poorly irAE treatment. However, interpreting neuronal antibody tests in diagnosis requires caution: positive results must align clinical context, some (e.g., SCLC) may have asymptomatic low levels, false are common without tissue-based confirmation. Also, use IL-6) lead more targeted treatments irAEs, minimizing effects compromising efficacy ICIs. This review provides comprehensive overview latest findings on associated focus prediction, prevention, well precision using autoantibodies, cytokines, microbiota. The most interesting data concern antibodies, which we explore pathogenic roles neurotoxicity. Most available both regarding role diagnostic prognostic supporting therapeutic decisions toxicities, refer non-neurological toxicities. our review, mention potential CXCL10 CXCL13 describe current evidence, need further studies, cytokines guiding selection second-line therapies n-irAEs. Finally, no specific microbiome-related microbial signature been proven linked specifically, leading future research topic.

Language: Английский

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