Autoimmune Endocrine Disease Related Antibodies Before the Start of Immune Checkpoint Inhibitor Therapy

Autoimmunity

Promising treatments have been added to the oncologist's arsenal in recent years. Treatments that, unlike conventional chemotherapy, do not aim to destroy cancer cells directly, but rather activate the patient's own immune system to recognize and attack tumor cells again. This new treatment is called immune checkpoint therapy. This involves administering antibodies (large Y-shaped proteins that can stick to the surface of cells) that remove the brakes from the immune system. The disadvantage of this innovative treatment is that the rejuvenated immune system can also attack cells that we want it not to recognize - our own body's cells. This is called autoimmunity. Patients who receive immune checkpoint therapy may suffer from symptoms such as skin rashes, diarrhea, hepatitis or hypothyroidism. The purpose of this study is to find biomarkers predictive of the development of these side effects, and possibly also predict a better outcome of the cancer therapy. The investigators will also look for the presence of antibodies against the endocrine glands (glands that produce hormones, such as the thyroid, adrenal, pituitary, and pancreas) before the start of the immune therapy.

Immune checkpoint inhibitor therapy (ICI) is the current standard of care for many malignancies, due to its unique mechanism of action. These therapies release the brakes of the immune system by targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4, e.g., ipilimumab, tremelimumab), programmed cell death-1 (PD-1, e.g., cemiplimab, dostarlimab, pembrolizumab, nivolumab) or its ligand (PD-L1, e.g., atezolizumab, avelumab, durvalumab). The flip side of the coin are immune-related adverse events (IrAE), including skin, intestinal and endocrinological toxicity, although any organ system can potentially be affected. The prospective follow-up of the endocrine autoantibodies is an area of interest as the presence of thyroid autoantibodies is associated with the occurrence of thyroiditis with immunotherapy. In turn, the occurrence of thyroiditis with immunotherapy is related to improved oncologic prognosis. Therefore, it would be of value to analyze whether the presence of thyroid autoimmunity (with positive thyroperoxidase and/or thyroglobulin autoantibodies) before the start of immunotherapy could be a marker of improved oncologic prognosis and outcome. Furthermore, there is a gap in our knowledge of the impact of autoantibodies against less common endocrinopathies, such as hypophysitis (inflammation of the pituitary gland), adrenalitis (inflammation of the adrenal glands) or pancreas (type-1 like diabetes mellitus). Finding a prognostic factor for these types of endocrinopathy is equally important, as these patients may present with life-threatening endocrinopathy (adrenal crisis, diabetic ketoacidosis) and should be recognized and treated in a timely manner. The main purpose of the current study is to evaluate the association between the autoimmune endocrine disease-related antibodies, the development of endocrine irAE and the impact on the tumor response including progression-free survival and overall survival. For this study, the investigators aim to perform a blood sample before and during the immunotherapy, for the analysis of the autoimmune endocrine disease related antibodies (Ab): anti-thyroglobulin Ab (aTg), anti-thyroperoxidase Ab (aTPO), anti-TSH-receptor Ab (TSI), pituitary Ab, adrenal Ab, and anti-GAD. The included patients will be prospectively followed up.

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