Heterogeneity of Head and Neck Squamous Cell Carcinoma Stem Cells

Qian, Xu; Nie, Xiaobo; Wollenberg, Barbara; Sudhoff, Holger; Kaufmann, Andreas M.; Albers, Andreas

doi:10.1007/978-3-030-14366-4_2

Cited by 13 publications

(11 citation statements)

References 102 publications

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“…As expected, opposite conclusions were obtained when LRP5 gene was silenced, strongly verified the tumorigenic role of LRP5 in colorectal carcinogenesis. CSCs are more resistant to chemoradiation therapy and lead to the malignant progression, metastasis, recurrence and poor prognosis by regenerating and maintaining the heterogeneous phenotypes of tumours 5,47 . Abundant studies have revealed the intimate relation between the Wnt signalling and CSCs 46,48 .…”

Section: Discussionmentioning

confidence: 99%

LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer

Nie

Liu

et al. 2022

J Cellular Molecular Medi

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The overactivation of canonical Wnt/β‐catenin pathway and the maintenance of cancer stem cells (CSCs) are essential for the onset and malignant progression of most human cancers. However, their regulatory mechanism in colorectal cancer (CRC) has not yet been well demonstrated. Low‐density lipoprotein receptor‐related protein 5 (LRP5) has been identified as an indispensable co‐receptor with frizzled family members for the canonical Wnt/β‐catenin signal transduction. Herein, we show that activation of LRP5 gene promotes CSCs‐like phenotypes, including tumorigenicity and drug resistance in CRC cells, through activating the canonical Wnt/β‐catenin and IL‐6/STAT3 signalling pathways. Clinically, the expression of LRP5 is upregulated in human CRC tissues and closely associated with clinical stages of patients with CRC. Further analysis showed silencing of endogenous LRP5 gene is sufficient to suppress the CSCs‐like phenotypes of CRC through inhibiting these two pathways. In conclusion, our findings not only reveal a regulatory cross‐talk between canonical Wnt/β‐catenin signalling pathway, IL‐6/STAT3 signalling pathway and CD133‐related stemness that promote the malignant behaviour of CRC, but also provide a valuable target for the diagnosis and treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer

Nie

Liu

et al. 2022

J Cellular Molecular Medi

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“…Hence, targeting Wnt-signaling seems a promising treatment strategy to augment ICI in HNSCC given its role in carcinogenesis as well as in shaping the TME [ 92 ]. Multiple small molecule inhibitors have been developed and some have already entered clinical trials also for HNSCC ( Supplementary Table 1 ).…”

Section: Immunological Implications Of the Hnscc Molecular Landscapementioning

confidence: 99%

At the Crossroads of Molecular Biology and Immunology: Molecular Pathways for Immunological Targeting of Head and Neck Squamous Cell Carcinoma

Wondergem

Nijenhuis

Poell

et al. 2021

Front. Oral. Health

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Background: Recent advances in immunotherapy for head and neck squamous cell carcinoma (HNSCC) have led to implementation of anti-programmed death receptor 1 (PD-1) immunotherapy to standard of care for recurrent/metastatic HNSCC. However, the majority of tumors do not respond to these therapies, indicating that these tumors are not immunogenic or other immunosuppressive mechanisms might be at play.Aim: Given their role in carcinogenesis as well as in immune modulation, we discuss the relation between the STAT3, PI3K/AKT/mTOR and Wnt signaling pathways to identify potential targets to empower the immune response against HNSCC.Results: We focused on three pathways. First, STAT3 is often overactivated in HNSCC and induces the secretion of immunosuppressive cytokines, thereby promoting recruitment of immune suppressive regulatory T cells and myeloid-derived suppressor cells to the tumor microenvironment (TME) while hampering the development of dendritic cells. Second, PI3K/AKT/mTOR mutational activation results in increased tumor proliferation but could also be important in HNSCC immune evasion due to the downregulation of components in the antigen-processing machinery. Third, canonical Wnt signaling is overactivated in >20% of HNSCC and could be an interesting pleotropic target since it is related to increased tumor cell proliferation and the development of an immunosuppressive HNSCC TME.Conclusion: The molecular pathology of HNSCC is complex and heterogeneous, varying between sites and disease etiology (i.e., HPV). The in HNSCC widely affected signaling pathways STAT3, PI3K/AKT/mTOR and Wnt are implicated in some of the very mechanisms underlying immune evasion of HNSCC, thereby representing promising targets to possibly facilitate immunotherapy response.

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“…HNSCC is an immunosuppressive disease with phenotypic and functional intratumor cellular heterogeneity [16,17]. HNSCC tumors interfere with the immune system by employing many mechanisms that modulate functions of immune cells to develop immune evasion and immune escape (for more detailed information, please refer to reviews by Albers et al and Qian et al [18,19]).…”

Section: Immuno-oncology Features Of Hnsccmentioning

confidence: 99%

Insights into Nanomedicine for Immunotherapeutics in Squamous Cell Carcinoma of the head and neck

Fang

Zhu

et al. 2020

Int. J. Biol. Sci.

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Immunotherapies such as immune checkpoint blockade benefit only a portion of patients with head and neck squamous cell carcinoma. The multidisciplinary field of nanomedicine is emerging as a promising strategy to achieve maximal anti-tumor effect in cancer immunotherapy and to turn non-responders into responders. Various methods have been developed to deliver therapeutic agents that can overcome bio-barriers, improve therapeutic delivery into the tumor and lymphoid tissues and reduce adverse effects in normal tissues. Additional modification strategies also have been employed to improve targeting and boost cytotoxic T cell-based immune responses. Here, we review the state-of-the-art use of nanotechnologies in the laboratory, in advanced preclinical phases as well as those running through clinical trials assessing their advantages and challenges.

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Heterogeneity of Head and Neck Squamous Cell Carcinoma Stem Cells

Cited by 13 publications

References 102 publications

LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer

LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer

At the Crossroads of Molecular Biology and Immunology: Molecular Pathways for Immunological Targeting of Head and Neck Squamous Cell Carcinoma

Insights into Nanomedicine for Immunotherapeutics in Squamous Cell Carcinoma of the head and neck

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