The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine

Wuhan, China

The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine

Wuhan, China
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Bu L.-L.,The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine | Bu L.-L.,Wuhan University | Yu G.-T.,The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine | Deng W.-W.,The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine | And 11 more authors.
OncoImmunology | Year: 2016

Cumulative evidence suggests that constitutively activated signal transducer and activator of transcription (STAT3) may contribute to sustaining immunosuppressive status, and that inhibiting STAT3 signaling represents a potential strategy to improve antitumor immunity. In the present study, we observed that high levels phosphorylated of STAT3 are significantly associated with the markers for both myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in human head and neck squamous cell carcinoma (HNSCC). Additionally, we showed that targeting STAT3 signaling with a tolerable selective inhibitor S3I-201 significantly decreased immature myeloid cells such as MDSCs, TAMs and iDCs in genetically defined mice HNSCC model. These findings highlight that targeting STAT3 signaling may be effective to enhance antitumor immunity via myeloid suppressor cells in HNSCC. © 2016 Taylor & Francis Group, LLC.


Yu G.-T.,The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine | Bu L.-L.,The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine | Zhao Y.-Y.,The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine | Mao L.,The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine | And 5 more authors.
OncoImmunology | Year: 2016

Immature myeloid cells such as myeloid-derived suppressor cells (MDSCs) and M2 macrophages play a vital role in the tumor immune escape and tumor progression. Cytotoxic T lymphocyte-associated antigen 4 (CTLA4), as a negative immune checkpoint, is highly expressed in numerous solid tumors. However, precise functions of CTLA4 in head and neck squamous cell carcinoma (HNSCC) have not yet been elucidated. In this study, we demonstrated that the ratio of CD8+/CTLA4 can be used as a potential index with a clinical prognostic value for HNSCC. Using immunocompetent transgenic mouse model with spontaneous HNSCC, we directly observed that targeting CTLA4 decreases MDSCs and M2 macrophages and promotes T cell activation in both tumor microenvironment and macro-environment. In all, our study provides direct evidence in vivo and proposes a rationale for CTLA4 inhibition as a future therapeutic strategy in patients with HNSCC. © 2016 Taylor & Francis Group, LLC.


PubMed | The State Key Laboratory Breeding Base of Basic Science of Stomatology &Key Laboratory of Oral Biomedicine, Wuhan University and U.S. National Institutes of Health
Type: | Journal: Scientific reports | Year: 2016

Cancer stem cells (CSCs) are considered responsible for tumor initiation and chemoresistance. This study was aimed to investigate the possibility of targeting head neck squamous cell carcinoma (HNSCC) by NOTCH1 pathway inhibition and explore the synergistic effect of combining NOTCH inhibition with conventional chemotherapy. NOTCH1/HES1 elevation was found in human HNSCC, especially in tissue post chemotherapy and lymph node metastasis, which is correlated with CSCs markers. NOTCH1 inhibitor DAPT (GSI-IX) significantly reduces CSCs population and tumor self-renewal ability in vitro and in vivo. Flow cytometry analysis showed that NOTCH1 inhibition reduces CSCs frequency either alone or in combination with chemotherapeutic agents, namely, cisplatin, docetaxel, and 5-fluorouracil. The combined strategy of NOTCH1 blockade and chemotherapy synergistically attenuated chemotherapy-enriched CSC population, promising a potential therapeutic exploitation in future clinical trial.


PubMed | Wuhan University, U.S. National Institutes of Health and The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine
Type: Journal Article | Journal: Oncoimmunology | Year: 2016

Cumulative evidence suggests that constitutively activated signal transducer and activator of transcription (STAT3) may contribute to sustaining immunosuppressive status, and that inhibiting STAT3 signaling represents a potential strategy to improve antitumor immunity. In the present study, we observed that high levels phosphorylated of STAT3 are significantly associated with the markers for both myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in human head and neck squamous cell carcinoma (HNSCC). Additionally, we showed that targeting STAT3 signaling with a tolerable selective inhibitor S3I-201 significantly decreased immature myeloid cells such as MDSCs, TAMs and iDCs in genetically defined mice HNSCC model. These findings highlight that targeting STAT3 signaling may be effective to enhance antitumor immunity via myeloid suppressor cells in HNSCC.

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