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Immune checkpoints, their control by immunotherapy and ovarian cancer.

ABSTRACT: Immune checkpoints are new targets for manipulation of immunological control over malignant tumors. They provide an important means to manage especially recurrent and refractory cancers and those cancers where there is an unmet need such as recurrent melanoma, renal cell carcinoma and recurrent ovarian cancer. As a new development this subject is experiencing rapid progress and multiple avenues are opening up. However, there are many hurdles to overcome, requiring constant updating, especially for students of ovarian cancer, who are looking at it with much hope.

SUBMITTER: Bose CK

PROVIDER: S-EPMC5701579 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Immune checkpoints, their control by immunotherapy and ovarian cancer.

Bose Chinmoy K CK

Contemporary oncology (Poznan, Poland) 20170929 3

Immune checkpoints are new targets for manipulation of immunological control over malignant tumors. They provide an important means to manage especially recurrent and refractory cancers and those cancers where there is an unmet need such as recurrent melanoma, renal cell carcinoma and recurrent ovarian cancer. As a new development this subject is experiencing rapid progress and multiple avenues are opening up. However, there are many hurdles to overcome, requiring constant updating, especially f ...[more]

PMID: 29180924

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Project description:Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Targeting the immune checkpoints cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) with inhibitory antibodies has demonstrated effective and durable antitumor activity in subgroups of patients with cancer. The US Food and Drug Administration has approved several immune checkpoint inhibitors (ICPis) for the treatment of a broad spectrum of malignancies. Endocrinopathies have emerged as one of the most common immune-related adverse events (irAEs) of ICPi therapy. Hypophysitis, thyroid dysfunction, insulin-deficient diabetes mellitus, and primary adrenal insufficiency have been reported as irAEs due to ICPi therapy. Hypophysitis is particularly associated with anti-CTLA-4 therapy, whereas thyroid dysfunction is particularly associated with anti-PD-1 therapy. Diabetes mellitus and primary adrenal insufficiency are rare endocrine toxicities associated with ICPi therapy but can be life-threatening if not promptly recognized and treated. Notably, combination anti-CTLA-4 and anti-PD-1 therapy is associated with the highest incidence of ICPi-related endocrinopathies. The precise mechanisms underlying these endocrine irAEs remain to be elucidated. Most ICPi-related endocrinopathies occur within 12 weeks after the initiation of ICPi therapy, but several have been reported to develop several months to years after ICPi initiation. Some ICPi-related endocrinopathies may resolve spontaneously, but others, such as central adrenal insufficiency and primary hypothyroidism, appear to be persistent in most cases. The mainstay of management of ICPi-related endocrinopathies is hormone replacement and symptom control. Further studies are needed to determine (i) whether high-dose corticosteroids in the treatment of ICPi-related endocrinopathies preserves endocrine function (especially in hypophysitis), and (ii) whether the development of ICPi-related endocrinopathies correlates with tumor response to ICPi therapy.

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Immune checkpoints, their control by immunotherapy and ovarian cancer.

Publications

Immune checkpoints, their control by immunotherapy and ovarian cancer.

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