Thymic hyperplasia following double immune checkpoint inhibitor therapy in two patients with stage IV melanoma

Abstract

Hyperplasia of the thymus is commonly seen in myasthenia gravis and other autoimmune disorders. Thymic size also varies with age, corticosteroid use, infections, and inflammatory disease. Although thymic hyperplasia has been described following chemotherapy, there is no known association of true thymic hyperplasia with immune checkpoint inhibitor therapy. We present two cases of suspected true thymic hyperplasia in patients with stage IV melanoma who were treated with the combination of nivolumab and ipilimumab, which was complicated by immune‐related toxicity requiring corticosteroid therapy, and then subsequently also by secondary hypoadrenalism requiring replacement hydrocortisone. In one patient, histological and flurocytometric analyses of an incisional biopsy of the thymus revealed findings consistent with true thymic hyperplasia. In the other case, the stable fluorodeoxyglucose positron emission tomography/Computed tomography (FDG‐PET/CT) findings were consistent also with true thymic hyperplasia. These are the first described cases of true thymic hyperplasia following combination immune checkpoint inhibitor therapy for metastatic melanoma. We hypothesize that the true thymic hyperplasia in these cases results from initial lymphocyte depletion caused by intense corticosteroid therapy followed by rebound thymic hyperplasia during the period of relative hypocortisolism, which may have been aggravated by the onset of secondary hypoadrenalism.

Characterization of immune checkpoint inhibitor‐induced cardiotoxicity reveals interleukin‐17A as a driver of cardiac dysfunction after anti‐PD‐1 treatment

“…Thus, we hypothesized that T‐cell activation in remote immune‐related organs and subsequent remote cytokine production may mediate the observed cardiac dysfunction. Enhanced thymic activity following immune checkpoint inhibition has been shown previously in a case report, where thymic hyperplasia has been observed in patients (Mencel et al, 2019). Furthermore, ICI treatment of patients with thymoma has been associated with the development of myocarditis (Konstantina et al, 2019).…”

<p>Anlotinib Exerts Anti-Cancer Effects on KRAS-Mutated Lung Cancer Cell Through Suppressing the MEK/ERK Pathway</p>

“…The MEK/ERK signal is one of the MAPK pathways which can regulate multiple cellular processes, including proliferation, apoptosis and chemoresistance. 30,31 Recently, Yen and Ji D reported that KRAS mutation in lung cancer cells increased the levels of phosphorylated MEK and ERK, and then promoted proliferation and suppressed apoptosis in lung cancer cells. 6,32,33 MEK/ERK signaling plays an important role in KRAS mutant lung cancer cells.…”