Autoantibodies involved in primary and secondary adrenal insufficiency following treatment with immune checkpoint inhibitors

Helderman, Noah C.; Lucas, Minke W.; Blank, Christian U.

doi:10.1016/j.iotech.2023.100374

Cited by 4 publications

(7 citation statements)

References 95 publications

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“…To date, no consensus has been reached on the possible mechanisms underlying irAE-related AI. 31 Upon ICI treatment, pre-existing autoreactive helper CD4+ and cytotoxic CD8+ T cells may be activated, subsequently infiltrating and destroying the adrenal cortex. 18 AI-associated autoantibodies such as anti-21-hydroxylase autoantibody and anti-guanine nucleotide-binding protein G(olf) subunit alpha antibodies have been reported to be present in patients with irAE-related AI.…”

Section: Discussionmentioning

confidence: 99%

“…18 AI-associated autoantibodies such as anti-21-hydroxylase autoantibody and antiguanine nucleotide-binding protein G(olf) subunit alpha antibodies have been reported to be present in patients with irAE-related AI. [31][32][33] Cross-reactive T and B cells activated by the ectopic expression of tissue antigens from tumor cells following ICI treatment may attack both tumor cells and the adrenal or pituitary glands. 31 The efficiency of ICI treatment is mainly achieved by activated cytotoxic T cells, organ damage by autoreactive B cell autoantibodies initiated under T-cell activation, and abnormally enhanced T-cell activity in both the pituitary and adrenal glands, which may largely explain the increased treatment efficacy for irAE-related AI in patients with cancer.…”

Section: Discussionmentioning

confidence: 99%

“…[31][32][33] Cross-reactive T and B cells activated by the ectopic expression of tissue antigens from tumor cells following ICI treatment may attack both tumor cells and the adrenal or pituitary glands. 31 The efficiency of ICI treatment is mainly achieved by activated cytotoxic T cells, organ damage by autoreactive B cell autoantibodies initiated under T-cell activation, and abnormally enhanced T-cell activity in both the pituitary and adrenal glands, which may largely explain the increased treatment efficacy for irAE-related AI in patients with cancer. In future studies, an immunohumanized animal model will be used to explore the mechanism of AI-mediated ICI treatment efficacy.…”

Section: Discussionmentioning

confidence: 99%

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Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment

Zhang,

Wu,

Zhao

et al. 2024

CMAR

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Purpose Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy. Patients and methods Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test. Results Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group ( P <0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P =0.008; irAE-B vs non-irAE, P =0.020), Eastern Cooperative Oncology Group (ECOG) status ( P =0.045), tumor-node-metastasis (TNM) stage ( P =0.000), and treatment line ( P =0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P =0.009; irAE-B vs non-irAE, P =0.013), ECOG status ( P =0.007), TNM stage ( P =0.035), treatment line ( P =0.001) and treatment modality ( P =0.008) were independent predictors for OS. Conclusion IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment

Zhang,

Wu,

Zhao

et al. 2024

CMAR

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show abstract

“…To date, no consensus has been reached on the possible mechanisms underlying irAE-related AI. 31 Upon ICI treatment, pre-existing autoreactive helper CD4+ and cytotoxic CD8+ T cells may be activated, subsequently infiltrating and destroying the adrenal cortex. 18 AI-associated autoantibodies such as anti-21-hydroxylase autoantibody and antiguanine nucleotide-binding protein G(olf) subunit alpha antibodies have been reported to be present in patients with irAE-related AI.…”

Section: Discussionmentioning

confidence: 99%

“…To date, no consensus has been reached on the possible mechanisms underlying irAE-related AI(Helderman, Lucas, & Blank, 2023). Upon ICIs treatment, preexisting autoreactive helper CD4 + and cytotoxic CD8 + T cells may be activated, subsequently in ltrating and destroying the adrenal cortex(Wright et al, 2021).…”

mentioning

confidence: 99%

Immune-related adverse event-related adrenal insufficiency mediates immune checkpoint inhibitors efficacy for cancer treatment

Zhang,

Wu,

Zhao

et al. 2023

Preprint

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Purpose Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer. An increasing number of immune-related adverse events (irAEs) have been discovered with the widespread clinical application of ICIs, which appear to be associated with improved treatment efficacy in certain cancers. We aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy. Methods Patients were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test. Results One hundred and ninety-two patients with cancer including gastrointestinal, respiratory, and other cancers, who received ICIs were enrolled in this study. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P < 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs. non-irAE, P = 0.008; irAE-B vs. non-irAE, P = 0.020), ECOG status (P = 0.045), TNM stage (P = 0.000), and treatment line (P = 0.002) were independent predictors of PFS. Meanwhile, irAE status (irAE-A vs. non-irAE, P = 0.009; irAE-B vs. non-irAE, P = 0.013), ECOG status (P = 0.007), TNM stage (P = 0.035), treatment line (P = 0.001) and treatment modality (P = 0.008) were independent predictors for OS. Conclusions IrAE-related AI was significantly associated with better clinical outcomes in patients with cancer and is a potentially predictable marker for better ICI treatment efficacy.

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Challenges and pitfalls in the management of endocrine toxicities from immune checkpoint inhibitors: a case presentation of synchronous thyrotoxicosis and primary adrenal insufficiency in a melanoma patient

Spagnolo,

Campo,

Campennì

et al. 2024

Hormones

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Autoantibodies involved in primary and secondary adrenal insufficiency following treatment with immune checkpoint inhibitors

Cited by 4 publications

References 95 publications

Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment

Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment

Immune-related adverse event-related adrenal insufficiency mediates immune checkpoint inhibitors efficacy for cancer treatment

Challenges and pitfalls in the management of endocrine toxicities from immune checkpoint inhibitors: a case presentation of synchronous thyrotoxicosis and primary adrenal insufficiency in a melanoma patient

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