Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Inhibitors targeting the programmed cell death 1 (PD-1) immune checkpoint have improved MCC patient outcomes by boosting antitumor T cell immunity. Here, we identify PD-1 as a growth-promoting receptor intrinsic to MCC cells. In human MCC lines and clinical tumors, RT-PCR-based sequencing, immunoblotting, flow cytometry, and immunofluorescence analyses demonstrated PD-1 gene and protein expression by MCC cells. MCC-PD-1 ligation enhanced, and its inhibition or silencing suppressed, in vitro proliferation and in vivo tumor xenograft growth. Consistently, MCC-PD-1 binding to PD-L1 or PD-L2 induced, while antibody-mediated PD-1 blockade inhibited, protumorigenic mTOR signaling, mitochondrial (mt) respiration, and ROS generation. Last, pharmacologic inhibition of mTOR or mtROS reversed MCC-PD-1:PD-L1-dependent proliferation and synergized with PD-1 checkpoint blockade in suppressing tumorigenesis. Our results identify an MCC-PD-1-mTOR-mtROS axis as a tumor growth-accelerating mechanism, the blockade of which might contribute to clinical response in patients with MCC.

Acrokeratosis Paraneoplastica (Bazex Syndrome): A Case Report.

Acrokeratosis paraneoplastica Bazex is a rare paraneoplastic skin manifestation, typically causing acral psoriasiform lesions. Patients usually show erythematous hyperkeratosis with yellowish, adherent scales on the hands and feet or other acral locations such as ears or nose. We herein report a case of Bazex syndrome in a male patient, who was previously diagnosed with hepatocellular carcinoma. Our case report highlights this rare condition as early diagnosis may impact the patient's course of tumor disease and prognosis.

Feasibility and safety of using an automated decision support system for insulin therapy in the treatment of steroid-induced hyperglycemia in patients with acute graft-versus-host disease: A randomized trial.

Steroid-induced hyperglycemia (SIHG) has shown to independently increase the risk for mortality in patients with acute graft-versus-host disease, and it is still unclear whether SIHG might be a modifiable risk factor. Therefore, a feasibility trial was carried out aiming to evaluate the performance of a standardized decision support system (GlucoTab [GT]) for insulin therapy in patients with SIHG. A total of 10 hyperglycemic acute graft-versus-host disease patients were included and treated either with GT or standard of care during hospitalization. Follow-up duration was 6 months. Comparing the GT versus standard of care group, 364 versus 1,020 glucose readings were available during a median of 41 days (interquartile range [IQR] 22-89) and 101 days (IQR 55-147) of hospitalization. The median overall glucose levels were 151 mg/dL (123-192) versus 162 mg/dL (IQR 138-193) for GT and standard of care, respectively (P < 0.001); hypoglycemia rates were comparably low. Treatment of SIHG with an algorithm-based system for subcutaneous insulin was feasible and safe.