Purpose: We applied a unique method to identify genes expressed in whole blood that can serve as biomarkers to detect colorectal cancer (CRC). Experimental Design:Total RNA was isolated from 211blood samples (110 non-CRC,101CRC). Microarray and quantitative real-time PCR were used for biomarker screening and validation, respectively. Results: From a set of 31 RNA samples (16 CRC, 15 controls), we selected 37 genes from analyzed microarray data that differed significantly between CRC samples and controls (P < 0.05).We tested these genes with a second set of 115 samples (58 CRC, 57 controls) using quantitative real-time PCR, validating 17 genes as differentially expressed. Five of these genes were selected for logistic regression analysis, of which two were the most up-regulated (CDA and MGC20553) and three were the most down-regulated (BANK1, BCNP1, and MS4A1) in CRC patients. Logit

Background: The prognostic role of tumor-infiltrating lymphocytes (TILs) in esophageal cancer (EC) patients is controversial; therefore, we performed a meta-analysis to obtain a consensus. Methods:The PubMed, PubMed Central, Embase, Cochrane Library, and Web of Science databases were searched. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed effect or random effect models depending on the heterogeneity. Results: A total of 30 articles comprising 5,122 patients were included in this meta-analysis. High levels of generalized TIL infiltration were associated with better overall survival (OS) (HR =0.67, 95% CI: 0.47-0.95, P=0.02) in EC patients. High CD8+ T-cell infiltration and high CD4+ T-cell infiltration were associated with better OS (HR =0.68, 95% CI: 0.60-0.78, P<0.001; HR =0.70, 95% CI: 0.57-0.85, P<0.001, respectively). However, the pooled results showed that neither CD3+ nor FOXP3+ T-cell infiltration were associated with patient survival (P>0.05). Moreover, for esophageal squamous cell carcinoma (ESCC), high CD8+ T lymphocyte infiltration in the TN (Tumor nest) or TS (Tumor stroma) significantly predicted better OS (pooled HR =0.70, 95% CI: 0.57-0.85; P=0.001; pooled HR =0.77, 95% CI: 0.65-0.91; P=0.003). Conclusions: High levels of generalized TILs, high CD8+ T-cell infiltration and high CD4+ T-cell infiltration have the potential to serve as prognostic markers in EC patients. Moreover, high CD8+ TIL in TNs or TS can predict better OS in ESCC patients.

Several clinical trials have shown the safety and effectiveness of PD-1/PD-L1 inhibitors in neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC). However, 18–83% patients can benefit from it. In this study, we aimed to assess the association of PD-L1 expression, tumor mutation burden, copy number alteration (CNA, including copy number gain and loss) burden with the pathologic response to neoadjuvant PD-1 blockade and investigate the changes in the tumor immune microenvironment (TIME) during neoadjuvant immunotherapy in NSCLC. Pre-immunotherapy treatment tumor samples from twenty-nine NSCLC patients who received neoadjuvant immunotherapy with sintilimab, an anti-PD-1 drug, were subjected to targeted DNA sequencing and PD-L1 immunochemistry staining. The pathological response was positively correlated with tumor proportion score (TPS) of PD-L1 and negatively correlated with copy number gain (CNgain) burden. Of note, the combination of CNgain burden and TPS can better stratify major pathological response (MPR) patients than did CNgain or TPS alone. Whereas, TMB showed a limited correlation with pathological regression. Additionally, PD-1 blockade led to an increase in CD8+PD-1−T cells which was clinically relevant to MPR as evaluated by multiplex immunofluorescence. A significant reduction in CD19+ cells was observed in the Non-MPR group but not in the MPR group, indicating the involvement of B cells in improving neoadjuvant immunotherapy response in NSCLC. Together, our study provides new data for the correlation of PD-L1 expression and genomic factors with drug response in neoadjuvant immunotherapy settings in NSCLC. The changes of TIME may provide novel insight into the immune responses to neoadjuvant anti-PD-1 therapy.

Esophageal cancer (EC) is a common cancer and is histopathologically classified into esophageal squamous cell carcinoma and esophageal adenocarcinoma. EC is a worldwide public health issue because of late diagnosis and lack of effective therapy. In contrast to standard tumor biopsies, liquid biopsies are emerging as a tool which is minimally invasive that can complement or even substitute more classical approaches. Specifically, cell‐free DNA (cfDNA) has shown promise in cancer‐related clinical applications. Indeed, cfDNA has been shown to be an effective circulating biomarker for non‐invasive cancer diagnosis and monitoring of cancer patients. Although the clinical application of cfDNA has been reported on other cancers, few studies have evaluated its use in EC. Here, we review this relevant literature and discuss limitations and advantages of its application in the diagnosis and monitoring of EC.

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