ABSTRACT
Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.
Subject(s)
Animals , Humans , Mice , Adoptive Transfer , Antibodies, Blocking , Autoimmunity , Cell- and Tissue-Based Therapy , Lymphocytes , T-Lymphocytes , T-Lymphocytes, Cytotoxic , ZidovudineABSTRACT
Functioning adrenocortical oncocytomas are extremely rare and most reported patients are 40-60 yr of age. To our knowledge, only 2 cases of functioning adrenocortical oncocytomas have been reported in childhood. We report a case of functioning adrenocortical oncocytoma in a 14-yr-old female child presenting with virilization. She presented with deepening of the voice and excessive hair growth, and elevation of plasma testosterone and dehydroepiandrosterone sulfate. She had an adrenalectomy. The completely resected tumor composed predominantly of oncocytes without atypical mitosis and necrosis. A discussion of this case and a review of the literature on this entity are presented.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Adenoma, Oxyphilic/complications , Adrenal Cortex Neoplasms/complications , Adrenalectomy , Virilism/etiologyABSTRACT
Patients with metastatic renal cell carcinomas have a median survival of less than 1 year and a 0-20% 5-year survial. The immunotherapy agent interferon-alpha has consistently produced objective responses rarely exceeding 20% of treated patients. Moreover, in patients with metastases to brain, liver or bone, the prognosis is extremely poor. A 66-year-old man, with a right renal cell carcinoma, with metastases to lung and bone who had entered a remarkable complete radiological remission of the metastases to lung and bone by 82 months following interferon-alpha immunotherapy, underwent a nephrectomy. The patient has remained recurrence free for 16 months after the nephrectomy.