Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

Abstract

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs. In this study, we investigated the role of IL-10 in MM TAM development as well as the therapeutic application of IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated that IL-10 is overexpressed in MM BM and mediates M2-like polarization of TAMs in patient BM, 3D co-cultures in vitro, and mouse models. In turn, TAMs promote MM proliferation and drug resistance, both in vitro and in vivo. Moreover, inhibition of IL-10/IL-10R/STAT3 axis using a blocking IL-10R monoclonal antibody and STAT3 protein degrader/PROTAC prevented M2 polarization of TAMs and the consequent TAM-induced proliferation of MM, and re-sensitized MM to therapy, in vitro and in vivo. Therefore, our findings suggest that inhibition of IL-10/IL-10R/STAT3 axis is a novel therapeutic strategy with monotherapy efficacy and can be further combined with current anti-MM therapy, such as immunomodulatory drugs, to overcome drug resistance. Future investigation is warranted to evaluate the potential of such therapy in MM patients.

People
Sun, Jennifer
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Corradini, Stefan
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Azab, Feda
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Shokeen, Monica
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Muz, Barbara
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Miari, Katerina E.
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

Miari, Katerina E. and Williams, Mark T. S. (2024) Stromal bone marrow fibroblasts and mesenchymal stem cells support acute myeloid leukaemia cells and promote therapy resistance. British Journal of Pharmacology, 181 (2). pp. 216-237. ISSN 0007-1188

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Maksimos, Mina
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Diedrich, Camila
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Asare, Obed
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Alhallak, Kinan
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Park, Chaelee
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Lubben, Berit
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Chen, Yixuan
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Adebayo, Ola
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Bash, Hannah
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Kelley, Sarah
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Fiala, Mark
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Bender, Diane E.
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Zhou, Haibin
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Wang, Shaomeng
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Vij, Ravi
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Williams, Mark T. S.
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

Miari, Katerina E. and Williams, Mark T. S. (2024) Stromal bone marrow fibroblasts and mesenchymal stem cells support acute myeloid leukaemia cells and promote therapy resistance. British Journal of Pharmacology, 181 (2). pp. 216-237. ISSN 0007-1188

See full publications list
Kareem Azab, Abdel
Author

Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel (2024) IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma. Leukemia, 38 (11). pp. 2355-2365. ISSN 0887-6924

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Texts
Information
Title:
IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma
Creators:
Sun, Jennifer and Corradini, Stefan and Azab, Feda and Shokeen, Monica and Muz, Barbara and Miari, Katerina E. and Maksimos, Mina and Diedrich, Camila and Asare, Obed and Alhallak, Kinan and Park, Chaelee and Lubben, Berit and Chen, Yixuan and Adebayo, Ola and Bash, Hannah and Kelley, Sarah and Fiala, Mark and Bender, Diane E. and Zhou, Haibin and Wang, Shaomeng and Vij, Ravi and Williams, Mark T. S. and Kareem Azab, Abdel
Identification Number:
10.1038/s41375-024-02391-8
Date:
November 2024
Divisions:
College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Publisher:
Springer Nature
Library
URI:
https://pub.demo35.eprints-hosting.org/id/eprint/121
Item Type:
Article
Depositing User:
Unnamed user with email ejo1f20@soton.ac.uk
Date Deposited:
11 Jun 2025 16:35
Revision:
11
Last Modified:
12 Jun 2025 11:33
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