The Expression of PD-L1 and B7-H4 in Thymic Epithelial Tumor and Its Relationship With Tumor Immune-Infiltrating Cells

Abstract

BackgroundPD-L1 and B7-H4 have been reported to be expressed in various malignancies and are considered as promising prognostic factors and potential immunotherapy targets.MethodsWe analyzed the correlation between the expression of PD-L1 and B7-H4 transcriptomes and clinicopathological characteristics in 121 TET patients from The Cancer Genome Atlas (TCGA) database. The immune-infiltration levels in the TET microenvironment were estimated using ssGSEA and quanTiseq algorithms. We collected 80 TET cases from 2008 to 2015. PD-L1、B7-H4、FOXP3 and CD163 protein expression in tumor tissues were detected by immunohistochemistry.ResultsTCGA database showed PD-L1 mRNA levels can predict the OS (P = 0.018) and DFS (P = 0.033) of TET patients. B7-H4 mRNA levels were positively related to the World Health Organization (WHO) pathological classification (P = 0.003) but not correlated with patient prognosis. Immune infiltration analysis showed PD-L1 is positively correlated with Tregs and M2 macrophages, B7-H4 is positively correlated with Tregs. Patients with high PD-L1 and Tregs or M2 macrophages, high B7-H4 and Tregs had a worse prognosis. Immunohistochemistry showed PD-L1 expression was positively correlated with the WHO pathological classification and Masaoka stage (P = 0.025, 0.003) and high PD-L1 expression can predict the poor OS of patients (P = 0.043); B7-H4 was also positively correlated with WHO pathological classification and Masaoka stage (P = 0.036, 0.049). However, B7-H4 expression did not correlate with patient prognosis. Evaluation of co-expression patterns showed TET patients with a high-grade WHO pathological classification harbored a 44.4% co-expression of PD-L1 and B7-H4. In addition, we found the expression level of PD-L1 is positively correlated with FOXP3 and CD163 (P = 0.004, P = 0.029) and B7-H4 is positively correlated with FOXP3 (P = 0.037). High PD-L1 combined with High FOXP3 and High CD163, High B7-H4 combined with High FOXP3 can be used to predict the poor prognosis of TET patients (P = 0.026, 0.031, 0.028, respectively).ConclusionPD-L1 and B7-H4 were related to the aggressiveness of TET and their expression level can indicate the suppressive immune microenvironment. Combined with FOXP3 and CD163, PD-L1 and B7-H4 can indicate a poor prognosis of TET.

B7-H4 is a potential diagnostic and prognostic biomarker in colorectal cancer and correlates with the epithelial-mesenchymal transition

“…ssGSEA is a deconvolution algorithm that evaluates the level of immune cell infiltration in a sample based on the expression level of immune cell-specific marker genes [ 13 ]. We performed ssGSEA analysis of the enrichment scores of tumor immune cells in Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) patients from the TCGA dataset, an approach we have used before [ 14 ].…”

“…Slides were washed 3 times with phosphate-buffered saline (PBS) for 5 min each, then incubated with 10% normal goat serum to block nonspecific binding. The sections were subsequently incubated with a rabbit anti-human B7-H4 monoclonal antibody (1:400 dilution; clone number EP1165; Abcam, MA, USA) at 4 °C overnight and a DAKO EnVision detection system (K5007, Dako, Glostrup, Denmark) was used to perform the immunoassay as previously described [ 14 ]. Slides were counterstained with Mayer’s hematoxylin, dehydrated with serial dilution of alcohol, and mounted with neutral resin.…”

“…Two indicators (staining intensity and percentage of positive cells) were combined to provide a semi-quantitative score, and the product of these two indicators was used to provide the final IHC score (0 to 12). Based on the IHC score, the tissue staining pattern was defined as either low expression (IHC score = 0–3) or high expression (IHC score = 4–12) [ 14 ].…”

MIF as a potential diagnostic and prognostic biomarker for triple‐negative breast cancer that correlates with the polarization of M2 macrophages

“…MIF expression scores were assessed semi-quantitatively based on the intensity of staining (weak: 1; moderate: 2; strong: 3; extremely strong: 4) and the abundance of positive cells (≤5%: 0; 6%-25%: 1; 26%-50%: 2; 51%-75%: 3; and ≥76%: 4). 21 The final staining score was obtained by multiplying the intensity and the abundance of positive cells and was classified as low (0-8) or high (9)(10)(11)(12)(13)(14)(15)(16).…”

B7-H4 expression is upregulated by PKCδ activation and contributes to PKCδ-induced cell motility in colorectal cancer

“…The expansion of both neutrophil progenitors and T cells can be suppressed by B7-H4, resulting in immune suppression [ 5 – 7 ]. In numerous tumor tissues, B7-H4 is overexpressed and positively correlated with various clinicopathological features [ 8 – 13 ]. B7-H4 expression was found to be significantly higher in CRC tissues than in normal tissues and positively related to infiltration depth, lymph node metastasis and regulatory T cell (Treg) infiltration [ 14 , 15 ].…”