Dataset Information

Tackling of Immunorefractory Tumors by Targeting Alternative Immune Checkpoints.

ABSTRACT: Physiologically, well known or traditional immune checkpoints (ICs), such as CTLA-4 and PD-1, are in place to promote tolerance to self-antigens and prevent generation of autoimmunity. In cancer, the ICs are effectively engaged by the tumor cells or stromal ells from the tumor microenvironment through expression of cognate ligands for the ICs present on the cell surface of CD8⁺ T lymphocytes. The ligation of ICs on CD8⁺ T lymphocytes triggers inhibitory signaling pathways, leading to quiescence or an exhaustion of CD8⁺ T lymphocytes. This results in failure of immunotherapy. To overcome this, several FDA-approved therapeutic antibodies are available, but the clinical outcome is quite variable due to the resistance encountered through upregulated expression of alternate ICs such as VISTA, LAG-3, TIGIT and TIM-3. This review focuses on the roles played by the traditional as well as alternate ICs and the contribution of associated signaling pathways in generating such resistance to immunotherapy. Combinatorial targeting of traditional and alternate ICs might be beneficial for immune-refractory tumors.

SUBMITTER: Dulal D

PROVIDER: S-EPMC10216651 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tackling of Immunorefractory Tumors by Targeting Alternative Immune Checkpoints.

Dulal Dharmindra D Boring Andrew A Terrero David D Johnson Tiffany T Tiwari Amit K AK Raman Dayanidhi D

Cancers 20230516 10

Physiologically, well known or traditional immune checkpoints (ICs), such as CTLA-4 and PD-1, are in place to promote tolerance to self-antigens and prevent generation of autoimmunity. In cancer, the ICs are effectively engaged by the tumor cells or stromal ells from the tumor microenvironment through expression of cognate ligands for the ICs present on the cell surface of CD8<sup>+</sup> T lymphocytes. The ligation of ICs on CD8<sup>+</sup> T lymphocytes triggers inhibitory signaling pathways, ...[more]

PMID: 37345111

Similar Datasets

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

Tackling of Immunorefractory Tumors by Targeting Alternative Immune Checkpoints.

Publications

Tackling of Immunorefractory Tumors by Targeting Alternative Immune Checkpoints.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets