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Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of HNSCC with or without HPV infection.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) are the sixth most common cancer type in the world. Human papillomavirus (HPV) infection is an emerging risk factor for HNSCC. Immune infiltration of HNSCC is linked to therapeutic results. This article aimed to decide whether variations in HPV status affect immune infiltration, molecular mechanism, and how these results vary in HNSCC patients. We investigated the tumor-infiltrating immune cells (TIICs) and immune-related gene differences between HPV (+) and HPV (-) HNSCC. The gene expression quantification data of HNSCC and their clinical information were download from the TCGA database. Immune-related genes have been linked to the ImmPort platform. After analyzed of 22 TIICs in the HNSCC tumor environment by CIBERSORT and further assessment, lower memory B cell and higher T cell regulatory were connected with better HPV (-) HNSCC outcome, higher activated memory CD4 T cell, higher T cell regulatory, and lower activated NK cell were linked with better HPV (+) result. We finally got five forms of immune genes (CAMP, EDNRB, NTS, CXCL9, LHB) associated with HNSCC progression. Higher expressions of CAMP, EDNRB, and NTS were associated with increased overall survival in HPV (-) patients. Higher expression of CXCL9 and lower expression of LHB contributed to increased overall survival of HPV (+) patients. There tend to be discrepancies in the cell structure of TIICs and immune-related genes in HPV (-) and HPV (+) HNSCC. These variances are typically too crucial for the therapeutic outcome of the patient and the development of the tumor. In specific, our sample established these candidate immune cells and immune-related genes as candidate reservoirs for further researches.

SUBMITTER: Zhou D

PROVIDER: S-EPMC8129356 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundsOsteosarcomas are one of the most common primary malignant tumors of bone. It primarily occurs in children and adolescents, with the second highest incidence among people over 50 years old. Although there were immense improvements in the survival of patients with osteosarcoma in the past 30 years, targetable mutations and agents of osteosarcomas still have been generally not satisfactory. Therefore, it is of great importance to further explore the highly specialized immune environment of bone, genes related to macrophage infiltration and potential therapeutic biomarkers and targets.MethodsThe 11 expression data sets of OS tissues and the 11 data sets of adjacent non-tumorous tissues available in the GEO database GSE126209 were used to conduct immune infiltration analysis. Then, through WGCNA analysis, we acquired the co-expression modules related to Mast cells activated and performed the GO and KEGG enrichment analysis. Next, we did the survival prognosis analysis and plotted a survival curve. Finally, we analyzed the COX multivariate regression of gene expression on clinical parameters and drew forest maps for visualization by the forest plot package.ResultsOS disease-related immune cell populations, mainly Mast cells activated, have higher cell content (p = 0.006) than the normal group. Then, we identified co-expression modules related to Mast cells activated. In sum, a total of 822 genes from the top three strongest positive correlation module MEbrown4, MEdarkslateblue and MEnavajowhite2 and the strongest negative correlation module MEdarkturquoise. From that, we identified nine genes with different levels in immune cell infiltration related to osteosarcoma, eight of which including SORBS2, BAIAP2L2, ATAD2, CYGB, PAMR1, PSIP1, SNAPC3 and ZDHHC21 in their low abundance have higher disease-free survival probability than the group in their high abundances.ConclusionThese results could assist clinicians to select targets for immunotherapies and individualize treatment strategies for patients with OS.

Project description:The neutrophils exhibit both anti-tumor and pro-tumor effects in cancers. The correlation between neutrophils and tumor development in lung adenocarcinoma (LUAD) is still uncertain, possibly due to a lack of specific neutrophil infiltration evaluation methods. In this study, we identified 30 hub genes that were significantly associated with neutrophil infiltration in LUAD through data mining, survival analysis, and multiple tumor-infiltrating immune cells (TICs) analysis, including TIMER, CIBERSORT, QUANTISEQ, XCELL, and MCPCOUNTER. Consensus clustering analysis showed that these 30 hub genes were correlated with clinical features in LUAD. We further developed a neutrophil scoring system based on these hub genes. The neutrophil score was significantly correlated with prognosis and tumor immune microenvironment (TIME) in LUAD. It was also positively associated with PD-L1 expression and negatively associated with tumor mutational burden (TMB). When combined with the neutrophil score, the predictive capacity of PD-L1 and TMB for prognosis was significantly improved. Thus, the 30 hub genes might play an essential role in the interaction of neutrophils and LUAD, and the neutrophil scoring system might effectually assess the infiltration of neutrophils. Furthermore, we verified the expression of these 30 genes in the LUAD tumor tissues collected from our department. We further found that overexpressed TNFAIP6 and TLR6 and downregulated P2RY13, SCARF1, DPEP2, PRAM1, CYP27A1, CFP, GPX3, and NCF1 in LUAD tissue might be potentially associated with neutrophils pro-tumor effects. The following in vitro experiments demonstrated that TNFAIP6 and TLR6 were significantly overexpressed, and P2RY13 and CYP27A1 were significantly downregulated in LUAD cell lines, compared to BEAS-2B cells. Knocking down TNFAIP6 in A549 and PC9 resulted in the upregulation of FAS, CCL3, and ICAM-1, and the downregulation of CCL2, CXCR4, and VEGF-A in neutrophils when co-culturing with the conditioned medium (CM) from LUAD cells. Knocking down TNFAIP6 in LUAD also led to an elevated early apoptosis rate of neutrophils. Therefore, overexpressed TNFAIP6 in LUAD cancer cells might lead to neutrophils "N2" polarization, which exhibited pro-tumor effects. Further research based on the genes identified in this pilot study might shed light on neutrophils' effects on LUAD in the future.

Project description:BackgroundEven though immunotherapy has been an effective treatment for solid tumors, its efficacy in osteosarcoma remains sub-optimal. It is therefore imperative to understand the complex tumor microenvironment (TME) of osteosarcoma to facilitate the development of immunotherapies against this cancer.MethodsThe mRNA expression profiles of osteosarcoma tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Next, the ssGSEA, MCP-counter, CIBERSORT, and Xcell algorithm analyses were performed to characterize the tumor microenvironment of osteosarcoma tissues. The tumor tissues were divided into inflammatory and non-inflammatory. A comprehensive assessment of immune cell infiltration in osteosarcoma tissues was then performed. Sub-group analysis of immune cell infiltration between men and women patients with osteosarcoma was also carried out.ResultsThe results revealed that the infiltration of immune cells including activated B cell, activated CD8 T cell, CD56dim natural killer cell, and cytotoxic lymphocytes cells, in osteosarcoma tissues was higher in male than in female patients. Based on the infiltration profile of different immune cells, the osteosarcoma tissues were grouped into four clusters. The four clusters were further divided into hot and cold tumors. The differently expressed genes (DEGs) between cold and hot tumors were mainly associated with the activation and regulation of immune response. Additionally, a neuronal pentraxin (NPTX2) expression which was upregulated in cold tumors was found to be negatively correlated with the expression of CD8a Molecule (CD8A), Granzyme B (GZMB), and Interferon Gamma (IFNG). NPTX2 decreased CCL4 secretion. Knockdown of NPTX2 in osteosarcoma cells inhibited tumor growth and increased tumor cell apoptosis. Moreover, a prognosis prediction model of osteosarcoma was constructed and validated in patients receiving immunotherapy using external data.ConclusionsTo the best of our knowledge, this is the first study to characterize the infiltration of immune cells in osteosarcoma tissues from patients receiving immune infiltration therapy.

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Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of HNSCC with or without HPV infection.

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