Risk factors for immune-related adverse events: what have we learned and what lies ahead?

Liu, Xiaoyan; Shi, Yuequan; Zhang, Dongming; Zhou, Qing; Liu, Jia; Chen, Minjiang; Xu, Yan; Zhao, Jing; Zhong, Wei; Wang, Mengzhao

doi:10.1186/s40364-021-00314-8

Cited by 48 publications

(46 citation statements)

References 187 publications

(277 reference statements)

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“…The work by Berner et al supports the first hypothesis, as they found nine antigens shared between both the tumor and skin tissue [ 99 ]. Furthermore, many iAREs are associated with B and T-cell responses [ 104 , 105 ]. However, some studies also point the finger at myeloid-driven inflammation as a source of iAREs.…”

Section: Do Polyamines Prevent Autoimmune-mediated Eradication Of Tum...mentioning

confidence: 99%

Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity

Chia

Zolp

Miska

2022

Cells

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Polyamines are ubiquitous, amine-rich molecules with diverse processes in biology. Recent work has highlighted that polyamines exert profound roles on the mammalian immune system, particularly inflammation and cancer. The mechanisms by which they control immunity are still being described. In the context of inflammation and autoimmunity, polyamine levels inversely correlate to autoimmune phenotypes, with lower polyamine levels associated with higher inflammatory responses. Conversely, in the context of cancer, polyamines and polyamine biosynthetic genes positively correlate with the severity of malignancy. Blockade of polyamine metabolism in cancer results in reduced tumor growth, and the effects appear to be mediated by an increase in T-cell infiltration and a pro-inflammatory phenotype of macrophages. These studies suggest that polyamine depletion leads to inflammation and that polyamine enrichment potentiates myeloid cell immune suppression. Indeed, combinatorial treatment with polyamine blockade and immunotherapy has shown efficacy in pre-clinical models of cancer. Considering the efficacy of immunotherapies is linked to autoimmune sequelae in humans, termed immune-adverse related events (iAREs), this suggests that polyamine levels may govern the inflammatory response to immunotherapies. This review proposes that polyamine metabolism acts to balance autoimmune inflammation and anti-tumor immunity and that polyamine levels can be used to monitor immune responses and responsiveness to immunotherapy.

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Section: Do Polyamines Prevent Autoimmune-mediated Eradication Of Tum...mentioning

confidence: 99%

Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity

Chia

Zolp

Miska

2022

Cells

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“…Autoantibodies have been recognized as risk factors for irAEs, for example, TPO-Ab in thyroid dysfunction and islet antibodies in ICI-induced DM [99] . This is possibly because ICIs could both facilitate preexisting autoantibody-mediated immunity and trigger the production of autoantibodies by enhancing B-cell immunity [114] .…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

Liu

Shi

Liu

et al. 2022

Translational Oncology

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“…Considering immune-related adverse events related to anti-PD-1 mAbs administration and the success of PD-1 gene inactivation in primary human T cells, this strategy was extended to CAR-T cell therapy ( 326 ). Hu B. et al, designed CAR-T cells directed against CD133 and KO for the PD-1 gene by using the CRISPR/Cas9 technology, with an average of 91.5% of inactivated gene sites.…”

Section: Challenges and Engineering Strategies To Overcome Car-t Cell...mentioning

confidence: 99%

Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment

et al. 2022

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During this last decade, adoptive transfer of T lymphocytes genetically modified to express chimeric antigen receptors (CARs) emerged as a valuable therapeutic strategy in hematological cancers. However, this immunotherapy has demonstrated limited efficacy in solid tumors. The main obstacle encountered by CAR-T cells in solid malignancies is the immunosuppressive tumor microenvironment (TME). The TME impedes tumor trafficking and penetration of T lymphocytes and installs an immunosuppressive milieu by producing suppressive soluble factors and by overexpressing negative immune checkpoints. In order to overcome these hurdles, new CAR-T cells engineering strategies were designed, to potentiate tumor recognition and infiltration and anti-cancer activity in the hostile TME. In this review, we provide an overview of the major mechanisms used by tumor cells to evade immune defenses and we critically expose the most optimistic engineering strategies to make CAR-T cell therapy a solid option for solid tumors.

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Risk factors for immune-related adverse events: what have we learned and what lies ahead?

Cited by 48 publications

References 187 publications

Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity

Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment

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