The tumor microenvironment (TME) has attracted attention owing to its essential role in tumor initiation, progression, and metastasis. With the emergence of immunotherapies for various cancers, and their high efficacy, an understanding of the TME in gastric cancer (GC) is critical. The aim of this study was to investigate the effect of various components within the GC TME, and to identify mechanisms that exhibit potential as therapeutic targets. The ESTIMATE algorithm was used to quantify immune and stromal components in GC samples, whose clinicopathological significance and relationship with predicted outcomes were explored. Low tumor mutational burden and high M2 macrophage infiltration, which are considered immune suppressive characteristics and may be responsible for unfavorable prognoses in GC, were observed in the high stromal group (HR = 1.585; 95% CI, 1.112-2.259; P = 0.009). Furthermore, weighted correlation network, differential expression, and univariate Cox analyses were used, along with machine learning methods (LASSO and SVM-RFE), to reveal genome-wide immune phenotypic correlations. Eight stromal-relevant genes cluster (FSTL1, RAB31, FBN1, ANTXR1, LRRC32, CTSK, COL5A2, and ENG) were identified as adverse prognostic factors in GC. Finally, using a combination of TIMER database and single-sample gene set enrichment analyses, we found that the identified genes potentially contribute to macrophage recruitment and polarization of tumor-associated macrophages. These findings provide a different perspective into the immune microenvironment and indicate potential prognostic and therapeutic targets for GC immunotherapies.
Gastric cancer (GC) is a common malignancy with low 5-year overall survival (OS).Recently, immune therapy has been used to treat cancer. B7H5 and CD28H are novel immune checkpoint molecules. However, the prognostic value of B7H5/CD28H expression in patients with GC remains unclear. In this study, seventy-one patients diagnosed with GC were included in this study. Patients' GC tissues and matched adjacent tissue constructed a tissue microarray. The expression levels of B7H5 and CD28H were examined using immunohistochemistry. Correlations between the expression of B7H5 and CD28H and the clinical data were evaluated. We found that the expression of B7H5 and CD28H (both P = .001) were higher in GC tumour tissues than in adjacent noncancerous tissues. B7H5/CD28H expression acted as an independent predictive factor in the OS of patients with GC. High expression of B7H5 and CD28H predicted poor outcome.Patients in the B7H5+CD28H+ group had a lower 5-year OS compared with patients in the B7H5−CD28− group (4.5% vs 55.6%, P = .001). A significant difference was found in the 5-year OS between patients in the B7H5+CD28H− and B7H5+CD28H+ groups (33.5% vs 4.5%, P = .006). However, there was no correlation between B7H5 and CD28H expression (P = .844). Therefore, B7H5 and CD28H expression are up-regulated in GC and are independent prognostic factors for overall survival in patients with GC. Although there was no correlation between B7H5 and CD28H expression, high expression of B7H5 and CD28H predicts poor prognosis, especially when both are highly expressed. K E Y W O R D SB7 family checkpoints, B7H5, CD28H, gastric cancer, immunotherapy
Background: There are still controversies between the curative effect of acupuncture combined with cupping therapy and western medicine for post-herpetic neuralgia (PHN). Our meta-analysis fully incorporates the research of acupuncture combined with cupping therapy versus Western medicine for PHN, aiming to explore the difference in the efficacy of the 2 therapies, so as to provide guidance for clinical treatment.Methods: We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, CBM, from establishment of the database to September, 2020. Include studies that are clearly defined as PHN or herpes zoster, and exclude duplicate publications; studies with no full text, incomplete information, or inability to extract data; the definition of exposure is quite different from most literature; animal experiments.Results: The total effective rate (relative ratio [RR] = 1.21, 95% confidence interval [CI]: 1.12-1.31) and the rate of remarkable effect (RR = 1.46, 95% CI: 1.30-1.63) of acupuncture and moxibustion combined with cupping in the treatment of PHN were significantly higher than that of conventional western medicine. The visual analogue scale score of acupuncture and moxibustion combined with cupping for PHN was significantly lower than that of conventional western medicine treatment (WMD = -1.77, 95% CI [-2.79, -0.75]). In addition, acupuncture and moxibustion combined with cupping therapy significantly reduced the occurrence of PHN compared with conventional western medicine treatment after treatment of acute herpes zoster (RR = 0.30, 95% CI: 0.20-0.45). In order to explore the differences in the efficacy and preventive effects of different types of acupuncture and cupping therapy, we have further conducted a subgroup analysis. Conclusion:The effect of acupuncture and moxibustion combined with cupping in the treatment of PHN is significantly higher than that of conventional western medicine, and it can significantly prevent the occurrence of PHN. Chinese medicine should be used more widely in the treatment of PHN.Abbreviations: PHN = post-herpetic neuralgia, RR = relative ratio, VAS = visual analogue scale/score.
Melanoma, which evolves from melanocytes, is the most malignant skin cancer and is highly fatal, although it only accounts for 4% of all skin cancers. Numerous studies have demonstrated that melanoma has a large tumor mutational burden, which means that melanoma has great potential to achieve immune evasion. Tumor-associated macrophages (TAMs) are an important component of both the immune system and tumor microenvironment. Several studies have demonstrated their double-edged sword effects on melanoma. The present review focuses on the role of TAMs in melanoma development, including regulation of proliferation, invasion, metastasis, angiogenesis and chemical resistance of melanoma. Furthermore, the existing mechanisms of action of the TAM-targeting treatments for melanoma are reviewed. More broadly, the weak points of existing research and the direction of future research are finally identified and described. Contents 1. Introduction 2. Overview of macrophages in the TME 3. Double-edged sword effect of TAMs in melanoma 4. TAM-targeting therapies in melanoma 5. Conclusion and future perspectives
Background: Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells. Methods: We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the “Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data” algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database. Results: The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values. Conclusions: The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.
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