Dataset Information

Double Guard Efficiency and Safety-Overcoming Resistance to Immunotherapy by Blocking or Stimulating Several Immune Checkpoints in Non-Small Cell Lung Cancer Patients.

ABSTRACT: Immunotherapy is one of the leading systemic therapies in non-small cell cancer (NSCLC) patients, but it is not effective in an important proportion of them due to primary or secondary resistance mechanisms. Clinicians do not have the tools to predict immunotherapy resistance, and thus, many patients still fail initial treatment. One of the scientific concepts to avoid resistance and/or offer the patient effective salvage second-line treatment is the dual immunologic checkpoint blockade. We aimed to review published and available data on combination immunotherapy in terms of mechanisms, efficacy, and safety data on many different dual blockades. We discussed the potential of combined CTLA-4 (Cytotoxic T Lymphocyte Antigen 4), PD-1 (Programmed Death 1) or PD-L1, TIGIT, LAG-3, TIM-3, macrophage leukocyte immunoglobulin-like receptor B2 (LILRB2/ILT4), S15-mediated immune suppression (SIGLEC-15), CD137, ICOS, and OX40 inhibitors in NSCLC treatment.

SUBMITTER: Kalinka E

PROVIDER: S-EPMC10341137 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Double Guard Efficiency and Safety-Overcoming Resistance to Immunotherapy by Blocking or Stimulating Several Immune Checkpoints in Non-Small Cell Lung Cancer Patients.

Kalinka Ewa E Wojas-Krawczyk Kamila K Krawczyk Paweł P

Cancers 20230705 13

Immunotherapy is one of the leading systemic therapies in non-small cell cancer (NSCLC) patients, but it is not effective in an important proportion of them due to primary or secondary resistance mechanisms. Clinicians do not have the tools to predict immunotherapy resistance, and thus, many patients still fail initial treatment. One of the scientific concepts to avoid resistance and/or offer the patient effective salvage second-line treatment is the dual immunologic checkpoint blockade. We aime ...[more]

PMID: 37444609

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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.

Dataset Information

Double Guard Efficiency and Safety-Overcoming Resistance to Immunotherapy by Blocking or Stimulating Several Immune Checkpoints in Non-Small Cell Lung Cancer Patients.

Publications

Double Guard Efficiency and Safety-Overcoming Resistance to Immunotherapy by Blocking or Stimulating Several Immune Checkpoints in Non-Small Cell Lung Cancer Patients.

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