Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment

Mun, Jeong-Yeon; Leem, Sun‐Hee; Lee, Jun Ho; Kim, Hyuk Soon

doi:10.3389/fimmu.2022.864739

Cited by 59 publications

(42 citation statements)

References 179 publications

(167 reference statements)

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“…Most of stromal elements, if not all, jointly contribute toward forming of an immunosuppressive TME that enables cancer cells to evade surveillance and attack from body’s immune system (Fig. 5 ) [ 244 ].…”

Section: Stromal Elements and The Immune Systemmentioning

confidence: 99%

Targeting the tumor stroma for cancer therapy

et al. 2022

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Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part of the tumor microenvironment, the tumor stroma is highly dynamic, heterogeneous and commonly tumor-type specific, and it mainly includes noncellular compositions such as the extracellular matrix and the unique cancer-associated vascular system as well as a wide variety of cellular components including activated cancer-associated fibroblasts, mesenchymal stromal cells, pericytes. All these elements operate with each other in a coordinated fashion and collectively promote cancer initiation, progression, metastasis and therapeutic resistance. Over the past few decades, numerous studies have been conducted to study the interaction and crosstalk between stromal components and neoplastic cells. Meanwhile, we have also witnessed an exponential increase in the investigation and recognition of the critical roles of tumor stroma in solid tumors. A series of clinical trials targeting the tumor stroma have been launched continually. In this review, we introduce and discuss current advances in the understanding of various stromal elements and their roles in cancers. We also elaborate on potential novel approaches for tumor-stroma-based therapeutic targeting, with the aim to promote the leap from bench to bedside.

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Section: Stromal Elements and The Immune Systemmentioning

confidence: 99%

Targeting the tumor stroma for cancer therapy

et al. 2022

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“…In addition, we found that stromal cell levels, including endothelial cells and fibroblasts, in high-risk tumors were significantly higher than those in low-risk tumors. Endothelial cells and fibroblasts are important cells that constitute the tumor microenvironment and can promote the occurrence and development of tumors ( Mun et al, 2022 ). The poor prognosis of high-risk tumors may also be related to the increase in these cells in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis-Related genes in the prognosis of colorectal cancer and their correlation with the tumor microenvironment

Dong

et al. 2022

Front. Genet.

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Colorectal cancer (CRC) is a common tumor disease of the digestive system with high incidence and mortality. Cuproptosis has recently been found to be a new form of cell death. The clinical significance of cuproptosis-related genes (CRGs) in CRC is not clear. In this study, The Cancer Genome Atlas Colon and Rectal Cancer dataset was used to analyze the relationship between CRGs and clinical characteristics of CRC by differential expression analysis and Kaplan–Meier survival (K-M) analysis. Based on CRGs, prognosis model and risk score of CRC was constructed in COADREAD by multivariate Cox analysis. Receiver operating curves (ROC) analysis, K-M analysis and calibration analysis in GDC TCGA Colon Cancer dataset were applied to validating model. Subsequently, the relationship between risk score of CRC and immune microenvironment was analyzed by multiple immune score algorithms. Finally, we found that most CRGs were differentially expressed between tumors and normal tissues. Some CRGs were differentially expressed among different clinical characteristics. K-M analysis showed that the CRGs were related to overall survival (OS), disease-specific survival, and progression-free survival. Subsequently, DLAT and CDKN2A were identified as risk factors for OS in CRC by multivariate Cox analysis, and the risk score was established. K–M analysis showed that there was a significant difference in OS between the high-risk and low-risk groups, which were grouped by risk score median. ROC analysis showed that the risk score performs well in predicting the 1-year, 3-year and 5-year OS. Enrichment analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immune-related signaling pathways. Further analysis showed that there were significant differences in the levels of immune cells and stromal cells between the high- and low-risk groups. The high-risk group had higher levels of immune cells and interstitial cells. At the same time, the high-risk group had a higher immune escape ability, and the predicted immune treatment response in the high-risk group was poor. In conclusion, CRGs can be used as prognostic factors in CRC and are closely related to the levels of immune cells and stromal cells in the tumor microenvironment.

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“…Te results of univariate and multivariate Cox regression Te TME is highly complex, and the study of TME can help provide new ideas for the treatment of tumors [18]. Stromal cells and immune cells are two important cell members of the TME [19]. Stromal cells have been demonstrated to be closely associated with the growth, metastasis, drug resistance of several cancers [20][21][22], and immune cells, depending on their type, can play an important role in fghting tumors and in promoting tumor progression or immune escape, respectively [23,24].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Myc-Regulated Gene Signature for Patients with Kidney Renal Clear Cell Carcinoma

Liu

Zhang

et al. 2022

Journal of Oncology

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Given that myc was known to be a cancer-causing gene in several cancers including kidney renal clear cell carcinoma (KIRC). We aimed to construct myc-regulated genes (MRGs)-based prognostic signature. We obtained the mRNA expression and clinical data of KIRC from The Cancer Genome Atlas (TCGA) database and MRGs from the Molecular Signature Database (MSigDB). Then, a prognostic signature consisting of 8 MRGs (IRF9, UBE2C, YBX3, CDKN2B, CKAP2L, CYFIP2, FBLN5, and PDLIM7) was developed by differential expression analysis, cox regression analysis, and least absolute shrinkage and selection operator (lasso) analysis. Patients with KIRC were divided into high- and low-risk groups based on risk scores of MRGs-based signatures. Patients in the high-risk group showed inferior clinical characteristics and survival. In addition, the risk score was an independent prognostic factor for KIRC, and the risk score=based nomogram displayed satisfactory performance to predict the survival of KIRC. The MRGs-based signature is also correlated with immune cell infiltration and the mRNA expression of important immune checkpoints (IDO2, PDCD1, LAG3, FOXP3, and TIGIT). The tumor mutation burden (TMB) landscape between the high- and low-risk groups showed higher levels of TMB in the high-risk group than in the low-risk group and that higher levels of TMB predicted a poorer prognosis in KIRC. Furthermore, patients with KIRC in the high-risk group are more likely to experience immune escape. At last, we found patients with KIRC in the high-risk group were more sensitive to several chemotherapy drugs such as sunitinib, gefitinib, nilotinib, and rapamycin than patients with KIRC in the low-risk group. Our study successfully constructed and validated an MRGs-based signature that can predict clinical characteristics, prognosis, level of immune infiltration, and responsiveness to immunotherapy and chemotherapy drugs in patients with KIRC.

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Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment

Cited by 59 publications

References 179 publications

Targeting the tumor stroma for cancer therapy

Targeting the tumor stroma for cancer therapy

Cuproptosis-Related genes in the prognosis of colorectal cancer and their correlation with the tumor microenvironment

Identification of a Novel Myc-Regulated Gene Signature for Patients with Kidney Renal Clear Cell Carcinoma

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