Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti–PD-1 in patients with PD-1–refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1 in a subset of PD-1 advanced melanoma.
Posttransplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent uncommon complications of transplantation and can lead to significant morbidity and mortality. PTLD is most prevalent during the first year following transplantation and occurs most frequently in multiorgan transplant recipients, followed by bowel, heart-lung, and lung recipients. It may involve any of the organ systems, with disease manifestation and the anatomic pattern of organ involvement being highly dependent on the type of transplantation. The current classification system includes four subtypes that have different prognoses requiring different treatment strategies. Tissue sampling is necessary for diagnosis and further subcategorization. The majority of cases are characterized by B-cell proliferation and are related to infection from Epstein-Barr virus. Knowledge of the distribution and radiologic features of PTLD allows the radiologist to play a pivotal role in making an early diagnosis and in guiding biopsy.
Understanding the characteristic appearances of primary gallbladder carcinoma at multiple imaging modalities can facilitate diagnosis and enable more accurate staging for triage to extended resection or an alternate therapy.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The macroscopic growth pattern of HCC is subdivided into three categories: nodular, massive, and infiltrative. Infiltrative HCC accounts for 7%-20% of HCC cases and is confirmed at pathologic analysis on the basis of the spread of minute tumor nodules throughout large regions of the liver. Infiltrative HCC may represent a diagnostic challenge because it is often difficult to distinguish from background changes in cirrhosis at imaging. Infiltrative HCC usually spreads over multiple hepatic segments, occupying an entire hepatic lobe or the entire liver, and it is frequently associated with portal vein tumor thrombosis. The tumor is usually ill defined at ultrasonography and shows minimal and inconsistent arterial enhancement and heterogeneous washout at contrast material-enhanced computed tomography and magnetic resonance (MR) imaging. The tumor may be more visible among the surrounding liver parenchyma at diffusion-, T1-, and T2-weighted MR imaging. Several liver diseases can mimic the infiltrative appearance of this malignancy, including focal confluent fibrosis, hepatic fat deposition, hepatic microabscesses, intrahepatic cholangiocarcinoma, and diffuse metastatic disease (pseudocirrhosis). The prognosis for patients with infiltrative HCC is poor because the tumor is often markedly advanced and associated with vascular invasion at presentation. Survival after surgical resection is decreased; thus, infiltrative HCC is a contraindication for resection and transplantation. Knowledge of the key tumor characteristics and imaging findings will help radiologists formulate a correct and timely diagnosis to improve patient management.
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