scholarly journals Role of the tumor immune microenvironment in tumor immunotherapy (Review)

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Changsheng Zhou ◽  
Qianqian Liu ◽  
Yi Xiang ◽  
Xin Gou ◽  
Wengang Li
Keyword(s):  
Tumor Immunotherapy ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

scholarly journals Alteration in the immune microenvironment based on APC status in MSS/pMMR colon cancer data retrieved from TCGA

2020 ◽  
Author(s):  
Haishan Lin ◽  
Hongchao Zhen ◽  
Kun Shan ◽  
Xiaoting Ma ◽  
Bangwei Cao
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Enrichment Analysis ◽  
Tumor Immunotherapy ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Cancer Data ◽  
T Cell Infiltration ◽  
Colon Cancers ◽  
Tumor Immune Microenvironment

Abstract Immunotherapy is currently the most advanced anti-tumor treatment approach. The efficacy of anti-tumor immunotherapy is closely related to the tumor immune microenvironment, including immune cells, infiltration of immune factors, and expression of immune checkpoints. At present, the biomarkers for predicting the efficacy of colon cancer immunotherapy do not cover all colon cancer patients suitable for immunotherapy. In this study, TCGA database was used to identify tumor genotypes suitable for anti-tumor immunotherapy. We found that some of the MSS/pMMR populations, that were initially considered unsuitable for immunotherapy, might actually be suitable. In APC-wt/MSS colon cancer, the expression of PD-1, PD-L1, CTLA4 and CYT（GZMA and PRF1）were increased. Based on calculations done by ESTIMATE and CIBERSORT algorithms, the ImmunoScore and the proportion of CT8+ T cell infiltration is increased in these patients. Enrichment analysis was done to screen signaling pathways involved in immune response, extracellular matrix, and cell adhesion. Tumors from 42 colon cancer patients, including 22 APC-mt/MSS and 20 APC-wt/MSS, were immunohistochemically evaluated for expression of CD8 and PD-L1. And APC-wt/MSS tumors showed significantly higher expression of CD8 and PD-L1 than APC-mt/MSS tumor. Based on the results, we found that some colon cancers of APC-wt/MSS are classified by Tumor Immune Microenvironment types (TIMTs) TMIT I. So that we speculate that APC-wt/MSS colon cancer patients could benefit from anti-tumor immunotherapy.

scholarly journals Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer

2021 ◽  
Author(s):  
Inga-Maria Launonen ◽  
Nuppu Lyytikäinen ◽  
Julia Casado ◽  
Ella Anttila ◽  
Angéla Szabó ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Single Cell ◽  
Single Cells ◽  
High Grade ◽  
Prognostic Role ◽  
Immune Microenvironment ◽  
Proteomic Data ◽  
Tumor Immune Microenvironment ◽  
Cellular Phenotypes

Abstract The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation of the BRCA1/2 genes. We aimed to discover how BRCA1/2 mutations shape the cellular phenotypes and spatial interactions of the tumor microenvironment. Using a highly multiplex immunofluorescence and image analysis we generated spatial proteomic data for 21 markers in 124,623 single cells from 112 tumor cores originating from 31 tumors with BRCA1/2 mutation (BRCA1/2mut), and from 13 tumors without alterations in HR genes (HRwt). We identified a phenotypically distinct tumor microenvironment in the BRCA1/2mut tumors with evidence of increased immunosurveillance. Importantly, we found an opposing prognostic role of a proliferative tumor-cell phenotypic subpopulation in the HR-genotypes, which associated with enhanced spatial tumor-immune interactions by the CD8+ and CD4+T-cells in BRCA1/2mut tumors. The single-cell spatial landscapes indicate distinct patterns of spatial immunosurveillance with the premise to improve immunotherapeutic strategies and patient stratification in HGSC.

scholarly journals Sexual dimorphism and the role of estrogen in the immune microenvironment of liver metastases

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Simon Milette ◽  
Masakazu Hashimoto ◽  
Stephanie Perrino ◽  
Shu Qi ◽  
Michely Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Sexual Dimorphism ◽  
Liver Metastases ◽  
Suppressor Cells ◽  
Cytotoxic T Cell ◽  
Immune Microenvironment ◽  
Ovariectomized Mice ◽  
Cell Accumulation ◽  
Tumor Immune Microenvironment

AbstractLiver metastases (LM) remain a major cause of cancer-associated death and a clinical challenge. Here we explore a sexual dimorphism observed in the regulation of the tumor immune microenvironment (TIME) of LM, wherein the accumulation of myeloid-derived suppressor cells (MDSC) and regulatory T cells in colon and lung carcinoma LM is TNFR2-dependent in female, but not in male mice. In ovariectomized mice, a marked reduction is observed in colorectal, lung and pancreatic carcinoma LM that is reversible by estradiol reconstitution. This is associated with reduced liver MDSC accumulation, increased interferon-gamma (IFN-γ) and granzyme B production in CD8+ T cells and reduced TNFR2, IDO2, TDO and Serpin B9 expression levels. Treatment with tamoxifen increases liver cytotoxic T cell accumulation and reduces colon cancer LM. The results identify estrogen as a regulator of a pro-metastatic immune microenvironment in the liver and a potential target in the management of liver metastatic disease.

scholarly journals Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Xing ◽  
Guojing Ruan ◽  
Haiwei Ni ◽  
Hai Qin ◽  
Simiao Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Immune Microenvironment ◽  
Non Coding Rna ◽  
Tumor Immune Microenvironment ◽  
Downstream Gene Expression

MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.

scholarly journals Systematic pan-cancer landscape identifies CARM1 as a potential prognostic and immunological biomarker

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yingqi Qiu ◽  
Hao Wang ◽  
Peiyun Liao ◽  
Binyan Xu ◽  
Rong Hu ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Integrated Analysis ◽  
Regulation Of Transcription ◽  
Immune Microenvironment ◽  
Arginine Methyltransferase ◽  
Clinical Prognosis ◽  
Tumor Immune Microenvironment ◽  
Arginine Residues ◽  
Pan Cancer

Abstract Background Belonging to the protein arginine methyltransferase (PRMT) family, the enzyme encoded by coactivator associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of protein arginine residues, especially acts on histones and other chromatin related proteins, which is essential in regulating gene expression. Beyond its well-established involvement in the regulation of transcription, recent studies have revealed a novel role of CARM1 in tumorigenesis and development, but there is still a lack of systematic understanding of CARM1 in human cancers. An integrated analysis of CARM1 in pan-cancer may contribute to further explore its prognostic value and potential immunological function in tumor therapy. Results Based on systematic analysis of data in multiple databases, we firstly verified that CARM1 is highly expressed in most tumors compared with corresponding normal tissues, and is bound up with poor prognosis in some tumors. Subsequently, relevance between CARM1 expression level and tumor immune microenvironment is analyzed from the perspectives of tumor mutation burden, microsatellite instability, mismatch repair genes, methyltransferases genes, immune checkpoint genes and immune cells infiltration, indicating a potential relationship between CARM1 expression and tumor microenvironment. A gene enrichment analysis followed shortly, which implied that the role of CARM1 in tumor pathogenesis may be related to transcriptional imbalance and viral carcinogenesis. Conclusions Our first comprehensive bioinformatics analysis provides a broad molecular perspective on the role of CARM1 in various tumors, highlights its value in clinical prognosis and potential association with tumor immune microenvironment, which may furnish an immune based antitumor strategy to provide a reference for more accurate and personalized immunotherapy in the future.

scholarly journals Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

2021 ◽  
Vol 8 ◽  
Author(s):  
Rui Li ◽  
Yun-Hong Yin ◽  
Xiu-Li Ji ◽  
Xiao Liu ◽  
Jian-Ping Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Rna Modification ◽  
Immune Microenvironment ◽  
Normal Tissues ◽  
Tumor Immune Microenvironment ◽  
Cancer Types ◽  
Pan Cancer

N6-methyladenosine RNA modification plays a significant role in the progression of multiple tumorigenesis. Our study identified the imperative role of m6A regulators in the tumor immune microenvironment, survival, stemness score, and anticancer drug sensitivity of pan-cancer. The Wilcox test was to identify the differential expression between 17 m6A regulators across 33 TCGA cancer types and their normal tissues from UCSC Xena GDC pan-cancer. Survival analysis of m6A-related regulators in 33 TCGA cancer types was identified using the “survival” and “survminer” package. The Spearman correlation test and Pearson correlation test were used to identify the correlation relationship between m6A regulators expression and tumor microenvironment, tumor stem cell score, and drug sensitivity of anticancer drugs. ConsensusPathDB was used for exploring m6A regulators functional enrichment. The 17 (METTL3, WTAP, METTL14, RBM15, RBM15B, VIRMA, HNRNPC, HNRNPA2B1, YTHDC1, ZC3H13, YTHDF1, YTHDC2, YTHDF2, IGF2BP3, IGF2BP1, FTO, and ALKBH5) m6A regulators were differentially expressed in 18 TCGA cancer types and adjacent normal tissues. Correlation analysis indicated that the relationship between the expression of 17 m6A regulators and tumor microenvironment indicated that the higher expression of m6A regulators, the higher the degree of tumor stem cells. The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin (p < 0.001). YTHDF2 expression was significantly negatively correlated with the anticancer drug dasatinib (p < 0.001). The pan-cancer immune subtype analysis showed that the 17 m6A regulators were significantly different in immune subtype C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte depleted), and C6 (TGF-beta dominant) (p < 0.001). Our study provides a comprehensive insight for revealing the significant role of m6A regulators in the tumor immune microenvironment, stemness score, and anticancer drug sensitivity of human cancers.

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