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Phenotypic Characterization by Single-Cell Mass Cytometry of Human Intrahepatic and Peripheral NK Cells in Patients with Hepatocellular Carcinoma.

ABSTRACT: Overall response rates of systemic therapies against advanced hepatocellular carcinoma (HCC) remain unsatisfactory. Thus, searching for new immunotherapy targets is indispensable. NK cells are crucial effectors and regulators in the tumor microenvironment and a determinant of responsiveness to checkpoint inhibitors. We revealed the landscape of NK cell phenotypes in HCC patients to find potential immunotherapy targets. Using single cell mass cytometry, we analyzed 32 surface markers on CD56^dim and CD56^bright NK cells, which included Sialic acid-binding immunoglobulin-type lectins (Siglecs). We compared peripheral NK cells between HCC patients and healthy volunteers. We also compared NK cells, in terms of their localizations, on an individual patient bases between peripheral and intrahepatic NK cells from cancerous and noncancerous liver tissues. In the HCC patient periphery, CD160⁺CD56^dim NK cells that expressed Siglec-7, NKp46, and NKp30 were reduced, while CD49a⁺CD56^dim NK cells that expressed Siglec-10 were increased. CD160 and CD49a on CD56^dim NK cells were significantly correlated to other NK-related markers in HCC patients, which suggested that CD160 and CD49a were signature molecules. CD49a⁺ CX3CR1⁺ Siglec-10⁺ NK cells had accumulated in HCC tissues. Considering further functional analyses, CD160, CD49a, CX3CR1, and Siglec-10 on CD56^dim NK cells may be targets for immunotherapies of HCC patients.

SUBMITTER: Yoshida Y

PROVIDER: S-EPMC8231799 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThe present study aimed to determine the reliable imaging features to distinguish atypical hepatocellular carcinoma (HCC) with peripheral rim-like enhancement from intrahepatic mass-forming cholangiocarcinoma (IMCC) on contrast-enhanced magnetic resonance imaging (MRI).MethodsA total of 168 patients (130 male, 57.10 ± 10.53 years) pathological confirmed HCC or IMCC who underwent contrast-enhanced MRI between July 2019 and February 2022 were retrospectively included. Univariate and multivariate logistic regression analyses were used to determine independent differential factors for distinguishing HCC from IMCC, and the model was established. Bootstrap resampling 1000 times was used to verify the model, which was visualized by nomograms. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical utility.ResultsRadiological capsule (OR 0.024, 95% CI: 0.006, 0.095, P<0.001), heterogeneous signal intensity (SI) on T1WI (OR 0.009, 95%CI: 0.001,0.056, P<0.001) were independent differential factors for predicting HCC over IMCC. A lobulated contour (OR 11.732, 95%CI: 2.928,47.007, P = 0.001), target sign on DP (OR 14.269, 95%CI: 2.849,82.106, P = 0.007), bile duct dilatation (OR 12.856, 95%CI: 2.013, P = 0.001) were independent differential factors for predicting IMCCs over HCCs. The independent differential factors constituted a model to distinguish atypical HCCs and IMCCs. The area under receiver operating characteristic (ROC) curve, sensitivity, and specificity values of the model were 0.964(0.940,0.987), 0.88, and 0.906, indicating that the model had an excellent differential diagnostic performance. The decision curve analysis (DCA) curve showed that the model obtained a better net clinical benefit.ConclusionThe present study identified reliable imaging features for distinguishing atypical HCCs with peripheral rim-like enhancement from IMCCs on contrast-enhanced MRI. Our findings may help radiologists provide clinicians with more accurate preoperative imaging diagnoses to select appropriate treatment options.

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Phenotypic Characterization by Single-Cell Mass Cytometry of Human Intrahepatic and Peripheral NK Cells in Patients with Hepatocellular Carcinoma.

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