Tumor Microenvironment
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2021 ◽  
Vol 12 ◽  
Yaping Chen ◽  
Xiao Zheng ◽  
Changping Wu

Colorectal cancer (CRC) has the second highest mortality rate among all cancers worldwide. Surgery, chemotherapy, radiotherapy, molecular targeting and other treatment methods have significantly prolonged the survival of patients with CRC. Recently, the emergence of tumor immunotherapy represented by immune checkpoint inhibitors (ICIs) has brought new immunotherapy options for the treatment of advanced CRC. As the efficacy of ICIs is closely related to the tumor immune microenvironment (TME), it is necessary to clarify the relationship between the immune microenvironment of CRC and the efficacy of immunotherapy to ensure that the appropriate drugs are selected. We herein review the latest research progress in the immune microenvironment and strategies related to immunotherapy for CRC. We hope that this review helps in the selection of appropriate treatment strategies for CRC patients.

2021 ◽  
Vol 12 ◽  
Zeng-Hong Wu ◽  
Dong-Liang Yang ◽  
Liang Wang ◽  
Jia Liu

BackgroundEpigenetics regulate gene expression without altering the DNA sequence. Epigenetics targeted chemotherapeutic approach can be used to overcome treatment resistance and low response rate in HCC. However, a comprehensive review of genomic data was carried out to determine the role of epigenesis in the tumor microenvironment (TME), immune cell-infiltration characteristics in HCC is still insufficient.MethodsThe association between epigenetic-related genes (ERGs), inflammatory response-related genes (IRRGs) and CRISPR genes was determined by merging genomic and CRISPR data. Further, characteristics of immune-cell infiltration in the tumor microenvironment was evaluated.ResultsNine differentially expressed genes (ANP32B, ASF1A, BCORL1, BMI1, BUB1, CBX2, CBX3, CDK1, and CDK5) were shown to be independent prognostic factors based on lasso regression in the TCGA-LIHC and ICGC databases. In addition, the results showed significant differences in expression of PDCD-1 (PD-1) and CTLA4 between the high- and low-epigenetic score groups. The CTRP and PRISM-derived drug response data yielded four CTRP-derived compounds (SB-743921, GSK461364, gemcitabine, and paclitaxel) and two PRISM-derived compounds (dolastatin-10 and LY2606368). Patients with high ERGs benefited more from immune checkpoint inhibitor (ICI) therapy than patients with low ERGs. In addition, the high ERGs subgroup had a higher T cell exclusion score, while the low ERGs subgroup had a higher T cell dysfunction. However, there was no difference in microsatellite instability (MSI) score among the two subgroups. Further, genome-wide CRISPR-based loss-of function screening derived from DepMap was conducted to determine key genes leading to HCC development and progression. In total, 640 genes were identified to be essential for survival in HCC cell lines. The protein-protein interaction (PPI) network demonstrated that IRRGs PSEN1 was linked to most ERGs and CRISPR genes such as CDK1, TOP2A, CBX2 and CBX3.ConclusionEpigenetic alterations of cancer-related genes in the tumor microenvironment play a major role in carcinogenesis. This study showed that epigenetic-related novel biomarkers could be useful in predicting prognosis, clinical diagnosis, and management in HCC.

2021 ◽  
Vol 12 ◽  
Changxi Han ◽  
Shaojian Lin ◽  
Xingyu Lu ◽  
Li Xue ◽  
Zhe Bao Wu

Macrophages are one of the most common infiltrating immune cells and an essential component of tumor microenvironment. Macrophages and the soluble cytokines and chemokines produced play an important role in tumorigenesis, progression, invasion and metastasis in solid tumors. Despite the multiple studies in other solid tumors, there is little known about macrophages in pituitary adenomas. Recently, studies about pituitary adenoma-infiltrated macrophages have been emerging, including the immunohistochemical and immunophenotypic analysis of the pituitary adenomas and further studies into the mechanism of the crosstalk between macrophages and tumor cells in vivo and in vitro. These studies have offered us new insights into the polarization of macrophages and its role in tumorigenesis, progression and invasion of pituitary adenomas. This review describes the advances in the field of pituitary adenoma-infiltrated macrophages and the prospect of targeting macrophages as cancer therapy in pituitary adenoma.

2021 ◽  
pp. 2106654
Jing Liu ◽  
Shasha He ◽  
Yingli Luo ◽  
Yue Zhang ◽  
Xiaojiao Du ◽  

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6052
Hongyan Xie ◽  
Jackson W. Appelt ◽  
Russell W. Jenkins

Recent advances in cancer immunotherapy have led a paradigm shift in the treatment of multiple malignancies with renewed focus on the host immune system and tumor–immune dynamics. However, intrinsic and acquired resistance to immunotherapy limits patient benefits and wider application. Investigations into the mechanisms of response and resistance to immunotherapy have demonstrated key tumor-intrinsic and tumor-extrinsic factors. Studying complex interactions with multiple cell types is necessary to understand the mechanisms of response and resistance to cancer therapies. The lack of model systems that faithfully recapitulate key features of the tumor microenvironment (TME) remains a challenge for cancer researchers. Here, we review recent advances in TME models focusing on the use of microfluidic technology to study and model the TME, including the application of microfluidic technologies to study tumor–immune dynamics and response to cancer therapeutics. We also discuss the limitations of current systems and suggest future directions to utilize this technology to its highest potential.

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