Abstract
Simple SummaryIn the past decade, the landscape of cancer treatment has radically changed after the introduction of immunotherapy. Adrenocortical carcinoma and metastatic pheochromocytoma/paraganglioma are rare cancers with limited responses to traditional cancer treatments. The use of immunotherapy against these cancers has yielded a few responses when used alone or in combination with other drugs. We reviewed the current literature to summarize the role of immunotherapy in these rare cancers.Adrenocortical cancers and metastatic pheochromocytomas are the most common malignancies originating in the adrenal glands. Metastatic paragangliomas are extra-adrenal tumors that share similar genetic and molecular profiles with metastatic pheochromocytomas and, subsequently, these tumors are studied together. Adrenocortical cancers and metastatic pheochromocytomas and paragangliomas are orphan diseases with limited therapeutic options worldwide. As in any other cancers, adrenocortical cancers and metastatic pheochromocytomas and paragangliomas avoid the immune system. Hypoxia-pseudohypoxia, activation of the PD-1/PD-L1 pathway, and/or microsatellite instability suggest that immunotherapy with checkpoint inhibitors could be a therapeutic option for patients with these tumors. The results of clinical trials with checkpoint inhibitors for adrenocortical carcinoma or metastatic pheochromocytoma or paraganglioma demonstrate limited benefits; nevertheless, these results also suggest interesting mechanisms that might enhance clinical responses to checkpoint inhibitors. These mechanisms include the normalization of tumor vasculature, modification of the hormonal environment, and vaccination with specific tumor antigens. Combinations of checkpoint inhibitors with classical therapies, such as chemotherapy, tyrosine kinase inhibitors, radiopharmaceuticals, and/or novel therapies, such as vaccines, should be evaluated in clinical trials.
Highlights
The adrenal glands are very important endocrine organs that are responsible for the regulation of many different physiological mechanisms that preserve human homeostasis and guarantee the individual’s survival
The study showed that 60% of tumors did not express PD-L1, and these patients exhibited shorter progression-free survival (PFS) and overall survival (OS) when compared with patients with PD-L1–positive tumors
The results of this study suggest that the combination of these two checkpoint inhibitors do not provide better responses than what is noticed in patients with
Summary
The adrenal glands are very important endocrine organs that are responsible for the regulation of many different physiological mechanisms that preserve human homeostasis and guarantee the individual’s survival. Most patients who underwent HSA-I-131-MIBG treatment had improved blood pressure compared to baseline, and the toxicity of HSA-I-131-MIBG was acceptable [22] This medication is only available in the United States and is not indicated for the treatment of patients with MPPGL that does not express the noradrenaline transporter [20]. Given this limited spectrum of therapeutic options, we need to identify other effective treatments for patients with ACC and MPPGL. We will discuss the rationale for the use of immunotherapy against ACC and MPPGL, the results of clinical trials with several checkpoint inhibitors against ACC and MPPGL, and potential mechanisms to induce or enhance an immune system response effective against ACC and MPPGL
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