Tumor-initiating stem cell shapes its microenvironment into an immunosuppressive barrier and pro-tumorigenic niche

Smith, Sarah E.; Chen, Shiyuan; Li, Hua; Wu, Di; Meneses-Giles, Paloma; Wang, Yongfu; Hembree, Mark; Yi, Kexi; Zhao, Xia; Guo, Fei; Unruh, Jay R.; Maddera, Lucinda; Yu, Zulin; Scott, Allison; Perera, Anoja; Wang, Yan; Zhao, Chongbei; Bae, KyeongMin; Box, Andrew; Haug, Jeffrey S.; Fang, Tao; Hu, Deqing; Hansen, Darrick M.; Qian, Pengxu; Saha, Subhrajit; Dixon, Dan A.; Anant, Shrikant; Zhang, Da; Lin, Edward H.; Sun, Weijing; Wiedemann, Leanne M.; Li, Linheng

doi:10.1016/j.celrep.2021.109674

Cited by 41 publications

(47 citation statements)

References 74 publications

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“…In addition to their transition processes already mentioned [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ], TME governs angiogenesis ( Figure 1 and Figure 2 ), a process of tumor growth by which new blood vessels develop from pre-existing ones. Angiogenesis depends on cancer EVs cooperation via their miRNAs and positive factors (vascular endothelial growth factor and matrix metalloproteinases), together with the suppression of another factor inhibiting the hypoxia-inducible factor [ 77 ].…”

Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

“…A TME, a dynamic milieu of stem and other types of cells, corresponds to the peculiar heterogeneous environment existing within niches. In addition, a TME is distributed in the spaces surrounding tumor masses [ 69 , 70 ]. For the development of cancer processes, such as migration and invasion, resistance to antitumor treatments, proliferation, and growth of metastases, CSCs are required to operate in the specific environment of TMEs, their immune agents, and other components [ 24 , 71 , 72 ].…”

Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

“…Recent studies have clarified processes by which cancer and non-cancer stem cells, during their navigation in the TME and upon their crosstalk, stimulate cancer development. An important contribution depends on the inhibition of immune cells by the so-called immune escape process [ 52 , 69 ]. Tumor-initiating CSCs shape their microenvironment into immunosuppressive barriers and pro-tumorigenic niches, all including filtered immune cells, which are most often macrophages and lymphocytes [ 69 , 70 ].…”

Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

“…An important contribution depends on the inhibition of immune cells by the so-called immune escape process [ 52 , 69 ]. Tumor-initiating CSCs shape their microenvironment into immunosuppressive barriers and pro-tumorigenic niches, all including filtered immune cells, which are most often macrophages and lymphocytes [ 69 , 70 ]. The interactions between macrophages and CSCs contribute to the development, association, and dissemination of tumor-associated cells dependent on the signaling of miRNAs released from EV cargoes [ 31 , 74 ].…”

Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

See 3 more Smart Citations

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Meldolesi

2022

IJMS

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Stem cells, identified several decades ago, started to attract interest at the end of the nineties when families of mesenchymal stem cells (MSCs), concentrated in the stroma of most organs, were found to participate in the therapy of many diseases. In cancer, however, stem cells of high importance are specific to another family, the cancer stem cells (CSCs). This comprehensive review is focused on the role and the mechanisms of CSCs and of their specific extracellular vesicles (EVs), which are composed of both exosomes and ectosomes. Compared to non-stem (normal) cancer cells, CSCs exist in small populations that are preferentially distributed to the niches, such as minor specific tissue sites corresponding to the stroma of non-cancer tissues. At niches and marginal sites of other cancer masses, the tissue exhibits peculiar properties that are typical of the tumor microenvironment (TME) of cancers. The extracellular matrix (ECM) includes components different from non-cancer tissues. CSCs and their EVs, in addition to effects analogous to those of MSCs/EVs, participate in processes of key importance, specific to cancer: generation of distinct cell subtypes, proliferation, differentiation, progression, formation of metastases, immune and therapy resistance, cancer relapse. Many of these, and other, effects require CSC cooperation with surrounding cells, especially MSCs. Filtered non-cancer cells, especially macrophages and fibroblasts, contribute to collaborative cancer transition/integration processes. Therapy developments are mentioned as ongoing preclinical initiatives. The preliminary state of clinical medicine is presented in terms of both industrial development and future treatments. The latter will be administered to specific patients together with known drugs, with the aim of eradicating their tumor growth and metastases.

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Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Meldolesi

2022

IJMS

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“…Tumours represent a complex and dynamic ecosystem of cells that are frequently transmitting and receiving signals, and this cross-talk can promote the growth of tumour cells and/or propagate the immunosuppressive TME. For example, the mapping of ligand–receptor signalling paths between tumour stem cells and TAMs highlighted a novel chemoradiotherapy-resistant mechanism driven by immunosuppressive PGE-2/EP-4 signalling [ 165 ]. In line with this theme, Zhang et al defined critical intercellular interactions between myeloid cells and the TME underpinning resistance to myeloid-targeted immunotherapies such as anti-CSF1R and CD40 agonists [ 166 ].…”

Section: Development Of Personalised Immunotherapies Guided By Integrated Omicsmentioning

confidence: 99%

Directing the Future Breakthroughs in Immunotherapy: The Importance of a Holistic Approach to the Tumour Microenvironment

Newnes

Armitage

Audsley

et al. 2021

Cancers

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Immunotherapy has revolutionised the treatment of cancers by exploiting the immune system to eliminate tumour cells. Despite the impressive response in a proportion of patients, clinical benefit has been limited thus far. A significant focus to date has been the identification of specific markers associated with response to immunotherapy. Unfortunately, the heterogeneity between patients and cancer types means identifying markers of response to therapy is inherently complex. There is a growing appreciation for the role of the tumour microenvironment (TME) in directing response to immunotherapy. The TME is highly heterogeneous and contains immune, stromal, vascular and tumour cells that all communicate and interact with one another to form solid tumours. This review analyses major cell populations present within the TME with a focus on their diverse and often contradictory roles in cancer and how this informs our understanding of immunotherapy. Furthermore, we discuss the role of integrated omics in providing a comprehensive view of the TME and demonstrate the potential of leveraging multi-omics to decipher the underlying mechanisms of anti-tumour immunity for the development of novel immunotherapeutic strategies.

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A Smart DNA Hydrogel Enables Synergistic Immunotherapy and Photodynamic Therapy of Melanoma

Yang,

Wu,

Wang

et al. 2024

Angewandte Chemie

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Immunotherapy faces insufficient immune activation and limited immune effectiveness. Herein, we report a smart DNA hydrogel that enables the release of multivalent functional units at the tumor site to enhance the efficacy of immunotherapy. The smart DNA hydrogel was assembled from two types of ultra‐long DNA chains synthesized via rolling circle amplification. One DNA chain contained immune adjuvant CpG oligonucleotides and polyaptamers for loading natural killer cell‐derived exosomes; the other chain contained multivalent G‐quadruplex for loading photodynamic agents. DNA chains formed DNA hydrogel through base‐pairing. HhaI restriction endonuclease sites were designed between functional units. Upon stimuli in the tumor sites, the hydrogel was effectively cleaved by the released HhaI and disassembled into functional units. Natural killer cell‐derived exosomes played an antitumor role, and the CpG oligonucleotide activated antigenpresenting cells to enhance the immunotherapy. Besides the tumorkilling effect of photodynamic therapy, the generated cellular debris acted as an immune antigen to further enhance the immunotherapeutic effect. In a mouse melanoma orthotopic model, the smart DNA hydrogel as a localized therapeutic agent, achieved a remarkable tumor suppression rate of 91.2%. The smart DNA hydrogel exhibited enhanced efficacy of synergistic immunotherapy and photodynamic therapy, expanding the application of DNA materials in biomedicine.

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Tumor-initiating stem cell shapes its microenvironment into an immunosuppressive barrier and pro-tumorigenic niche

Cited by 41 publications

References 74 publications

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Directing the Future Breakthroughs in Immunotherapy: The Importance of a Holistic Approach to the Tumour Microenvironment

A Smart DNA Hydrogel Enables Synergistic Immunotherapy and Photodynamic Therapy of Melanoma

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