Endocrine complications of cancer immunotherapy

Abstract

Immunotherapy using monoclonal antibodies -checkpoint inhibitors -is a dynamically evolving discipline of clinical oncology and a new hope for patients with advanced and disseminated cancer. However, the activation of T-lymphocytes can at the same time lead to autoimmune response and destruction of healthy organs, which is a serious adverse effect that can also affect the endocrine system. Here we present possible endocrine complications of immunotherapy with contemporary inhibitors of immune checkpoints (CTLA-4, PD-1, PD-L1/L2), their frequency, symptoms, and proposed grade-dependent treatment. Failure to diagnose endocrine pathology can in adverse circumstances lead to treatment failure and condemn the patient's fate. Due to tremendous progress in cancer immunotherapy during the last few years and an increase in the number of treated patients, endocrinologists should become acquainted with the specificity of this mode of oncological treatment. (Endokrynol Pol 2018; 69 (6): 722-733)  Endocrine complications of immunotherapy Aleksandra Król et al.

Anti‑PD‑1 immune checkpoint inhibitor inducing endocrine toxicity in a patient with advanced lung cancer: A case report and literature review

“…Limited information is available regarding the connection between anti-PD-1/PD-L1 therapy and severe endocrine toxicity (12). Immune-related endocrinopathies, including hypophysitis and hypothyroidism, are difficult to diagnose because of their nonspecific and rare symptoms (17).…”

“…Therefore, the patient's laboratory findings (including hyperglycemia, high serum ketone and low arterial blood pH) met the criteria for a diagnosis of DKA (17). After a comprehensive discussion and literature review, it was determined that the patient had pembrolizumab-induced autoimmune diabetes and DKA, which resulted in immunotherapy termination.…”

Common endocrine system adverse events associated with immune checkpoint inhibitors

“…PD-1 glycoprotein is a second inhibitory receptor that belongs to the immunoglobulin superfamily. 9 , 10 , 16 , 17 It is expressed on the surface of activated T lymphocytes, B lymphocytes, and monocytes/macrophages. CTLA-4 is molecularly linked to B7 (CD80/CD86), whereas PD-1 has specific ligands, PD-L1 and PD-L2 [ Figure 1 C].…”

Histamine in cancer immunology and immunotherapy. Current status and new perspectives

“…In particular, immunotherapy with immune checkpoint inhibitors using CTLA‐4, PD‐1, and PD‐L1 neutralizing or blocking antibodies is a promising and rapidly growing field of interest with impressive success in many solid tumors 207–210 . It seeks to unleash anti‐tumor T‐cell responses by avoiding host immunotolerance, and results in durable clinical responses but only in a fraction of patients 211,212 …”