Multiple Immune-Suppressive Mechanisms in Fibrolamellar Carcinoma.

Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that affects adolescents and young adults. The most effective treatment for FLC is surgical resection, but no standardized systemic therapy exists for patients with recurrent or unresectable FLC. As a first step to understand the immune microenvironment of FLC, we investigated targetable immune-checkpoint pathways, PD-1, PD-L1, B7-H3, IDO-1, and LAG3, in relation to CD8+ cytotoxic T-lymphocyte density. Thirty-two FLC tumor specimens were analyzed using IHC staining for PD-L1, CD8, PD-1, IDO, LAG3, and B7-H3. Sixty-three percent of FLC cases demonstrated membranous PD-L1 expression on tumor cells, and almost 70% of cases demonstrated PD-L1+ tumor-infiltrating lymphocytes and tumor-associated macrophages (TIL/TAM). Myeloid-derived cells appeared to be a major component of PD-L1+ tumor-infiltrating immune cells. Forty percent of the cases showed B7-H3 expression in the tumor zone, with 91% cases showing B7-H3 expression in TILs and TAMs. IDO and PD-1 expression was highest in the tumor interface zone. B7-H3 or IDO expression on tumor cells significantly correlated with higher CD8+ T-cell density. In conclusion, a high proportion of FLC cases showed robust expression of PD-1, PD-L1, B7-H3, and IDO in an adaptive immune-resistance pattern. Our findings provide further basis for targeting these different immune-checkpoint axes in FLC.

Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) includes minimal assessment of cognitive function, particularly in right hemisphere (RH) stroke. Descriptions of the Cookie Theft picture from the NIHSS allow analyses that (1) correlate with aphasia severity and (2) identify communication deficits in RH stroke. We hypothesized that analysis of the picture description contributes valuable information about volume and location of acute stroke. METHODS: We evaluated 67 patients with acute ischemic stroke (34 left hemisphere [LH]; 33 RH) with the NIHSS, analysis of the Cookie Theft picture, and magnetic resonance imaging, compared with 35 sex- and age-matched controls. We evaluated descriptions for total content units (CU), syllables, ratio of left:right CU, CU/minute, and percent interpretive CU, based on previous studies. Lesion volume and percent damage to regions of interest were measured on diffusion-weighted imaging. Multivariable linear regression identified variables associated with infarct volume, independently of NIHSS score, age and sex. RESULTS: Patients with RH and LH stroke differed from controls, but not from each other, on CU, syllables/CU, and CU/minute. Left:right CU was lower in RH compared with LH stroke. CU, syllables/CU, and NIHSS each correlated with lesion volume in LH and RH stroke. Lesion volume was best accounted by a model that included CU, syllables/CU, NIHSS, left:right CU, percent interpretive CU, and age, in LH and RH stroke. Each discourse variable and NIHSS score were associated with percent damage to different regions of interest, independently of lesion volume and age. CONCLUSIONS: Brief picture description analysis complements NIHSS scores in predicting stroke volume and location.