Implications of a granulocyte‐high glioblastoma microenvironment in immune suppression and therapy resistance †

KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer

Cancer Cell ◽

10.1016/j.ccell.2019.02.008 ◽

2019 ◽

Vol 35 (4) ◽

pp. 559-572.e7 ◽

Cited By ~ 72

Author(s):

Wenting Liao ◽

Michael J. Overman ◽

Adam T. Boutin ◽

Xiaoying Shang ◽

Di Zhao ◽

...

Keyword(s):

Colorectal Cancer ◽

Immune Suppression ◽

Immune Therapy ◽

Therapy Resistance

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Quantifying Cancer Epithelial-Mesenchymal Plasticity and its Association with Stemness and Immune Response

Journal of Clinical Medicine ◽

10.3390/jcm8050725 ◽

2019 ◽

Vol 8 (5) ◽

pp. 725 ◽

Cited By ~ 22

Author(s):

Dongya Jia ◽

Xuefei Li ◽

Federico Bocci ◽

Shubham Tripathi ◽

Youyuan Deng ◽

...

Keyword(s):

Cancer Cells ◽

Immune Suppression ◽

Epithelial Mesenchymal Transition ◽

Therapy Resistance ◽

Mesenchymal Transition ◽

Experimental Approaches ◽

Systematic Understanding ◽

Small Clusters ◽

Stable Hybrid

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial–mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e., the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression.

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Quantifying Cancer Epithelial-Mesenchymal Plasticity and Its Association with Stemness and Immune Response

10.20944/preprints201904.0206.v1 ◽

2019 ◽

Author(s):

Dongya Jia ◽

Xuefei Li ◽

Federico Bocci ◽

Shubham Tripathi ◽

Youyuan Deng ◽

...

Keyword(s):

Cancer Cells ◽

Immune Suppression ◽

Epithelial Mesenchymal Transition ◽

Therapy Resistance ◽

Mesenchymal Transition ◽

Experimental Approaches ◽

Systematic Understanding ◽

Small Clusters ◽

Stable Hybrid

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial-mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e. the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression.

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Macrophage Biology and Mechanisms of Immune Suppression in Breast Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.643771 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anita K. Mehta ◽

Sapana Kadel ◽

Madeline G. Townsend ◽

Madisson Oliwa ◽

Jennifer L. Guerriero

Keyword(s):

Breast Cancer ◽

Tumor Immunity ◽

Immune Suppression ◽

Therapy Resistance ◽

Adverse Outcomes ◽

Phenotypic Characterization ◽

Before And After ◽

Current Therapies ◽

Subset Diversity ◽

Future Work

Macrophages are crucial innate immune cells that maintain tissue homeostasis and defend against pathogens; however, their infiltration into tumors has been associated with adverse outcomes. Tumor-associated macrophages (TAMs) represent a significant component of the inflammatory infiltrate in breast tumors, and extensive infiltration of TAMs has been linked to poor prognosis in breast cancer. Here, we detail how TAMs impede a productive tumor immunity cycle by limiting antigen presentation and reducing activation of cytotoxic T lymphocytes (CTLs) while simultaneously supporting tumor cell survival, angiogenesis, and metastasis. There is an urgent need to overcome TAM-mediated immune suppression for durable anti-tumor immunity in breast cancer. To date, failure to fully characterize TAM biology and classify multiple subsets has hindered advancement in therapeutic targeting. In this regard, the complexity of TAMs has recently taken center stage owing to their subset diversity and tightly regulated molecular and metabolic phenotypes. In this review, we reveal major gaps in our knowledge of the functional and phenotypic characterization of TAM subsets associated with breast cancer, before and after treatment. Future work to characterize TAM subsets, location, and crosstalk with neighboring cells will be critical to counteract TAM pro-tumor functions and to identify novel TAM-modulating strategies and combinations that are likely to enhance current therapies and overcome chemo- and immuno-therapy resistance.

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