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Nutrient supplements from selected botanicals mediated immune modulation of the tumor microenvironment and antitumor mechanism

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Abstract

Specific extracts of selected vegetables (SV) have been shown to benefit the survival of stage IIIb/IV non-small cell lung cancer patients in phase I/II studies and is currently in a phase III trial. However, the underlying mechanism of SV-mediated antitumor immune responses has not been elucidated. Our results indicate that SV modulated the NK and adoptive T cell immune responses in antitumor efficacy. Furthermore, antitumor effects of SV were also mediated by innate myeloid cell function, which requires both TLR and β-glucan signaling in a MyD88/TRIF and Dectin-1-dependent manner, respectively. Additionally, SV treatment reduced granulocytic myeloid-derived suppressor cell (MDSC) infiltration into the tumor and limited monocytic MDSC toward the M2-like functional phenotype. Importantly, SV treatment enhanced antigen-specific immune responses by augmenting the activation of antigen-specific TH1/TH17 cells in secondary lymphoid organs and proliferative response, as well as by reducing the Treg population in the tumor microenvironment, which was driven by SV-primed activated M-MDSC. Our results support the idea that SV can subvert immune-tolerance state in the tumor microenvironment and inhibit tumor growth. The present study suggests that features, such as easy accessibility, favorable clinical efficacy, no detectable side effects and satisfactory safety make SV a feasible, appealing and convincing adjuvant therapy for the treatment of cancer patients and prevent tumor recurrence and/or metastases.

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The data analyzed and shown in presented study is available from the corresponding authors upon reasonable request.

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Acknowledgements

The authors thank Ms. Marcia Meseck for editing the manuscript. The authors thanks Dr. Jun Yan (University of Louisville) for providing the bone marrow of Dectin-1 KO C57BL/6 mice for this study.

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Authors and Affiliations

  1. Department of Oncological Sciences, Icahn School of Medicine At Mount Sinai, New York, 10029, USA

    Hui-Ming Chen, Ping-Ying Pan & Shu-Hsia Chen

  2. Immunotherapy Research Center, Houston Methodist Research Institute, Houston, TX, 77030, USA

    Hui-Ming Chen, Ping-Ying Pan & Shu-Hsia Chen

  3. Cancer Center, Houston Methodist Research Institute, Houston, 77030, USA

    Hui-Ming Chen, Ping-Ying Pan & Shu-Hsia Chen

  4. Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine Graduate School of Medical Sciences, New York, USA

    Shu-Hsia Chen

  5. Department of Ophthalmology, Columbia University, New York, 10027, USA

    Linus Sun

  6. Institute of Integrated Medicine and Chinese Medical Research Center, China Medical University, Taichung, 40402, Taiwan, ROC

    Lu-Hai Wang

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  1. Hui-Ming Chen
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  2. Linus Sun
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  4. Lu-Hai Wang
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Contributions

Dr. Hui-Ming Chen performed most of the research, analyzed data and wrote the manuscript; Dr. Linus Sun and Dr. Ping-Ying Pan made contributions to interpretation of data and intellectual content. Dr. Lu-Hai Wang and Dr. Shu-Hsia Chen made substantial contribution to the conception or design of the research, important intellectual content, project supervision and wrote the manuscript with valuable contribution from all other authors.

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Correspondence to Lu-Hai Wang or Shu-Hsia Chen.

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All animal experiments were done in accordance with approved guidelines for animal experimentation of the Mount Sinai School of Medicine.

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Chen, HM., Sun, L., Pan, PY. et al. Nutrient supplements from selected botanicals mediated immune modulation of the tumor microenvironment and antitumor mechanism. Cancer Immunol Immunother 70, 3435–3449 (2021). https://doi.org/10.1007/s00262-021-02927-2

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  • DOI: https://doi.org/10.1007/s00262-021-02927-2

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