ABSTRACT
Policy must address drivers, not just symptoms, of subsidence.
ABSTRACT
A major breakthrough in cancer immunotherapy was the discovery of immune checkpoint proteins, which function to effectively inhibit the immune system through various mechanisms. The first of such molecules shown to inhibit both T-cell proliferation and IL-2 production was cytotoxic T-lymphocyte associated protein 4 (CTLA-4). With this discovery, efforts turned to blocking this inhibitory pathway in an attempt to activate dormant T-cells directed at cancer cells. The first antibody directed against CTLA-4, ipilimumab, was quickly ushered into clinical trials and was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011. Following the success of ipilimumab, other immune checkpoints were studied as possible targets for inhibition. One such interaction was that of the programmed cell death-1 (PD-1) T-cell receptor and its ligand found on many cancer cells, programmed death-ligand 1 (PD-L1). Unfortunately, the untoward effects of blocking the immune system's natural inhibitory mechanisms have manifested clinically as diarrhea, rash, and hepatitis. Nevertheless, the exciting field of immune checkpoint inhibitors offers a potential curative option for many cancer patients who previously had a more dismal prognosis. The authors aim to provide a comprehensive review of the literature and update on the use of CTLA-4, PD-1 and PD-L1 targeted therapy in the treatment of cancer and other molecules still in the early development phase.
Subject(s)
Antibodies/therapeutic use , Antineoplastic Agents/therapeutic use , Drug Discovery/methods , Immunotherapy/methods , Molecular Targeted Therapy/methods , Neoplasms/drug therapy , Animals , Antibodies/adverse effects , Antineoplastic Agents/adverse effects , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Humans , Immunotherapy/adverse effects , Molecular Targeted Therapy/adverse effects , Neoplasms/immunology , Neoplasms/metabolism , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Signal Transduction/drug effects , Treatment OutcomeABSTRACT
A 61-year-old female with a past medical history significant for von Hippel-Lindau (VHL) syndrome presented with multiple bilateral pulmonary lesions found on surveillance computed tomography scan. Positron emission tomography demonstrated avidity in a lesion in the right upper lobe. After an equivocal biopsy, a lobectomy via a thoracoscopic approach was performed as this lesion was concerning for a primary lung cancer. Pathology revealed a diagnosis of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. To our knowledge, this is the first reported case of a pulmonary MALT lymphoma in a patient with VHL.
