The updated landscape of tumor microenvironment and drug repurposing

Jin, Ming; Jin, Wei

doi:10.1038/s41392-020-00280-x

Cited by 771 publications

(580 citation statements)

References 255 publications

(294 reference statements)

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“…In solid cancers, the TME can promote immunosuppressive mechanisms, tumor vascularization, growth, and metastasis [26][27][28]. The challenging heterogeneity and dynamic nature of solid tumors, as well as the inherent chemo-resistance present in many tumors, appear to be influenced considerably by the cellular composition of, and interactions within the TME [26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Characterization by Mass Cytometry of the Microenvironment in Ovarian Cancer and Impact of Tumor Dissociation Methods

Anandan

Thomsen

Gullaksen

et al. 2021

Cancers

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Improved molecular dissection of the tumor microenvironment (TME) holds promise for treating high-grade serous ovarian cancer (HGSOC), a gynecological malignancy with high mortality. Reliable disease-related biomarkers are scarce, but single-cell mapping of the TME could identify patient-specific prognostic differences. To avoid technical variation effects, however, tissue dissociation effects on single cells must be considered. We present a novel Cytometry by Time-of-Flight antibody panel for single-cell suspensions to identify individual TME profiles of HGSOC patients and evaluate the effects of dissociation methods on results. The panel was developed utilizing cell lines, healthy donor blood, and stem cells and was applied to HGSOC tissues dissociated by six methods. Data were analyzed using Cytobank and X-shift and illustrated by t-distributed stochastic neighbor embedding plots, heatmaps, and stacked bar and error plots. The panel distinguishes the main cellular subsets and subpopulations, enabling characterization of individual TME profiles. The dissociation method affected some immune (n = 1), stromal (n = 2), and tumor (n = 3) subsets, while functional marker expressions remained comparable. In conclusion, the panel can identify subsets of the HGSOC TME and can be used for in-depth profiling. This panel represents a promising profiling tool for HGSOC when tissue handling is considered.

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Section: Discussionmentioning

confidence: 99%

Phenotypic Characterization by Mass Cytometry of the Microenvironment in Ovarian Cancer and Impact of Tumor Dissociation Methods

Anandan

Thomsen

Gullaksen

et al. 2021

Cancers

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“…Understanding the breadth and the mechanisms of regulatory interactions within the TME is crucial to the development of novel therapeutic options against cancer as well as to a better understanding of the oncogenic process as a whole [37,38].…”

Section: Discussionmentioning

confidence: 99%

Machine Learning Identifies Robust Matrisome Markers and Regulatory Mechanisms in Cancer

Kääriäinen

Pesola

Dittmann

et al. 2020

IJMS

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The expression and regulation of matrisome genes—the ensemble of extracellular matrix, ECM, ECM-associated proteins and regulators as well as cytokines, chemokines and growth factors—is of paramount importance for many biological processes and signals within the tumor microenvironment. The availability of large and diverse multi-omics data enables mapping and understanding of the regulatory circuitry governing the tumor matrisome to an unprecedented level, though such a volume of information requires robust approaches to data analysis and integration. In this study, we show that combining Pan-Cancer expression data from The Cancer Genome Atlas (TCGA) with genomics, epigenomics and microenvironmental features from TCGA and other sources enables the identification of “landmark” matrisome genes and machine learning-based reconstruction of their regulatory networks in 74 clinical and molecular subtypes of human cancers and approx. 6700 patients. These results, enriched for prognostic genes and cross-validated markers at the protein level, unravel the role of genetic and epigenetic programs in governing the tumor matrisome and allow the prioritization of tumor-specific matrisome genes (and their regulators) for the development of novel therapeutic approaches.

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“…The clinical significance of aspirin use has also been demonstrated in colorectal cancer patients, particularly with PDL1 low tumors [ 176 , 177 ]. However, most of the clinical studies are retrospective, and the therapeutic efficacies of COX inhibitors remain to be determined in clinical settings [ 178 ]. Interestingly, one study reported that treatment with a CDK4/6 inhibitor palbociclib suppressed COX2/PGE2 by the repression of c-JUN expression, resulting in the suppression of cancer metastasis in mouse breast cancer models [ 161 ].…”

Section: Treatments For Cancer Metastasismentioning

confidence: 99%

Targeting Oncoimmune Drivers of Cancer Metastasis

Kudo-Saito¹,

Ozaki²,

Imazeki³

et al. 2021

Cancers

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Residual metastasis is a major cause of cancer-associated death. Recent advances in understanding the molecular basis of the epithelial–mesenchymal transition (EMT) and the related cancer stem cells (CSCs) have revealed the landscapes of cancer metastasis and are promising contributions to clinical treatments. However, this rarely leads to practical advances in the management of cancer in clinical settings, and thus cancer metastasis is still a threat to patients. The reason for this may be the heterogeneity and complexity caused by the evolutional transformation of tumor cells through interactions with the host environment, which is composed of numerous components, including stromal cells, vascular cells, and immune cells. The reciprocal evolution further raises the possibility of successful tumor escape, resulting in a fatal prognosis for patients. To disrupt the vicious spiral of tumor–immunity aggravation, it is important to understand the entire metastatic process and the practical implementations. Here, we provide an overview of the molecular and cellular links between tumors’ biological properties and host immunity, mainly focusing on EMT and CSCs, and we also highlight therapeutic agents targeting the oncoimmune determinants driving cancer metastasis toward better practical use in the treatment of cancer patients.

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The updated landscape of tumor microenvironment and drug repurposing

Cited by 771 publications

References 255 publications

Phenotypic Characterization by Mass Cytometry of the Microenvironment in Ovarian Cancer and Impact of Tumor Dissociation Methods

Phenotypic Characterization by Mass Cytometry of the Microenvironment in Ovarian Cancer and Impact of Tumor Dissociation Methods

Machine Learning Identifies Robust Matrisome Markers and Regulatory Mechanisms in Cancer

Targeting Oncoimmune Drivers of Cancer Metastasis

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