Viewing the immune checkpoint VISTA: landscape and outcomes across cancers.

BACKGROUND: Optimizing immune checkpoint inhibitor (ICI) therapy may require identification of co-targetable checkpoint pathways via immune profiling. Herein, we analyzed the transcriptomic expression and clinical correlates of V-domain immunoglobulin suppressor of T-cell activation (VISTA), a promising targetable checkpoint. PATIENTS AND METHODS: RNA sequencing was carried out on 514 tissues reflecting diverse advanced/metastatic cancers. Expression of eight immune checkpoint markers [lymphocyte-activation gene 3 (LAG-3), tumor necrosis factor receptor superfamily 14 (TNFRSF14), programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), B- and T-lymphocyte attenuator (BTLA), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cytotoxic T-lymphocyte antigen 4 (CTLA-4)], in addition to VISTA, was analyzed, along with clinical outcomes. RESULTS: High VISTA RNA expression was observed in 32% of tumors (66/514) and was the most common highly expressed checkpoint among the nine assessed. High VISTA expression was independently correlated with high BTLA, TIM-3, and TNFRSF14, and with a diagnosis of pancreatic, small intestine, and stomach cancer. VISTA transcript levels did not correlate with overall survival (OS) from metastatic/advanced disease in the pan-cancer cohort or with immunotherapy outcome (progression-free survival and OS from the start of ICI) in 217 ICI-treated patients. However, in ICI-treated pancreatic cancer patients (n = 16), median OS was significantly shorter (from immunotherapy initiation) for the high- versus not-high-VISTA groups (0.28 versus 1.21 years) (P = 0.047); in contrast, VISTA levels were not correlated with OS in 36 pancreatic cancer patients who did not receive ICI. CONCLUSION: High VISTA expression correlates with high BTLA, TIM-3, and TNFRSF14 checkpoint-related molecules and with poorer post-immunotherapy survival in pancreatic cancer, consistent with prior literature indicating that VISTA is prominently expressed on CD68+ macrophages in pancreatic cancers and requiring validation in larger prospective studies. Immunomic analysis may be important for individualized precision immunotherapy.

Diagnostic implications of MR imaging for mucinous adenocarcinoma arising from fistula in ano.

Mucinous adenocarcinoma associated with chronic fistula in ano is rare, and diagnosis is often difficult. Two cases of mucinous adenocarcinoma arising from fistula in ano occur in a patient with longlasting fistulas, persisting for more than 10 years, are presented. In two cases, T2-weighted MR images revealed symptomatic features; that is, the hyperintense heterogeneous content looked like a gathering of various sizes of granules. This is due to the fact that mucinous adenocarcinomas usually consist of the gathering of many small mucous lakes. This finding has the implications in diagnosing mucinous adenocarcinoma arising from carcinoma in ano.

An incidentally discovered small and asymptomatic para-aortic paraganglioma.

Preoperative diagnosis of asymptomatic paraganglioma is difficult due to the lack of specific symptoms. In this report, we present a rare case of a small and asymptomatic para-aortic paraganglioma. A 34-year-old woman who complained of back pain was admitted for further examination. No abnormal findings were observed on physical or laboratory examinations. An abdominal CT scan and an abdominal MRI incidentally noted a mass about 3 cm in diameter adjacent to the right edge of the inferior vena cava. The following aortic angiography showed the tumor with a feeding artery diverting directly from the aorta. The tumor was completely resected by laparotomy. The resected tumor, 3 x 3 x 3 cm in size, was soft, dark-reddish and encapsulated. Immunohistochemical examinations showed that it was positive for neuron-specific enolase, chromogranin A and adrenocorticotropin. Under these findings, the diagnosis of para-aortic paraganglioma was determined. Seven years after the operation, she remains asymptomatic and free of disease.