Myeloid signature reveals immune contexture and predicts the prognosis of hepatocellular carcinoma

Abstract

BACKGROUND. Despite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC). METHODS. Using in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri-and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts. RESULTS. The MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8 + T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC. CONCLUSION. We identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes.

Neutrophil Extracellular Traps and Macrophage Extracellular Traps Predict Postoperative Recurrence in Resectable Nonfunctional Pancreatic Neuroendocrine Tumors

“…Considering that the cumulative incidence of 3-year recurrence after resection reaches up to 26.5% ( 27 ) and that 2-year RFS is an important recurrence risk score group analysis time point ( 28 ), we selected 3-year survival as the observed long-term survival. Nomograms showed remarkably accurate clinical usefulness to predict recurrence and survival outcomes, superior to current predictive prognosis models ( 29 ). A nomogram was established to predict the 3-year recurrence-free probability ( Figure 2E ).…”

Phenotypic profiling and prognostic significance of immune infiltrates in esophageal squamous cell carcinoma

“…A lot of studies have taken full advantages of TMA to characterize TME. 46 Further studies on the whole tissue section would aid in showing the heterogeneity of ESCC TME. Secondly, we performed the multicolor staining in two panels separately, which forbade the spatial analysis of phenotypes in different panels, such as EC-CTL engagement level.…”

HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma

“…A total of 205 HCC patients who had received a tumor resection at the Sun Yat-sen University Cancer Center between 2006 and 2010 were enrolled in this study. 20 , 21 The inclusion criteria were as follows: no concurrent autoimmune disease, human immunodeficiency virus (HIV), or syphilis, as well as an absence of anticancer therapy or distant metastasis before surgery. All patients underwent an HCC curative resection with the following intra-operative aims: At least 1 cm in a resection margin, all tumor nodules were completely resected, and the cut surface free of tumor left (based on histological examination).…”