Converting lymphoma cells into potent antigen-presenting cells for interferon-induced tumor regression

Jing Liao; Yan Luan; Zhenhua Ren; Xiaojuan Liu; Diyuan Xue; Hairong Xu; Zhichen Sun; Kaiting Yang; Hua Peng; Yang Xin Fu

doi:10.1158/2326-6066.CIR-16-0221

Converting lymphoma cells into potent antigen-presenting cells for interferon-induced tumor regression

Jing Liao, Yan Luan, Zhenhua Ren, Xiaojuan Liu, Diyuan Xue, Hairong Xu, Zhichen Sun, Kaiting Yang, Hua Peng, Yang Xin Fu

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Anti-hCD20 is a therapeutic mAb that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-α (IFNα) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)- associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNα (anti-CD20-IFNα) depended on existing tumor-infiltrating CD8⁺ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APC) for the reactivation of tumor-infiltrating CD8⁺ T cells that then controlled those lymphomas. Anti-CD20-IFNα also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti-CD20-IFNα eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8⁺ T cells and synergizing with anti-PD-L1 treatment. Cancer Immunol Res; 5(7); 560-70.

Original language	English (US)
Pages (from-to)	560-570
Number of pages	11
Journal	Cancer Immunology Research
Volume	5
Issue number	7
DOIs	https://doi.org/10.1158/2326-6066.CIR-16-0221
State	Published - Jul 2017

ASJC Scopus subject areas

Immunology
Cancer Research

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10.1158/2326-6066.CIR-16-0221

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@article{0997e9daeada4ca28c929c7cea24d622,

title = "Converting lymphoma cells into potent antigen-presenting cells for interferon-induced tumor regression",

abstract = "Anti-hCD20 is a therapeutic mAb that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-α (IFNα) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)- associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNα (anti-CD20-IFNα) depended on existing tumor-infiltrating CD8+ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APC) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Anti-CD20-IFNα also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti-CD20-IFNα eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8+ T cells and synergizing with anti-PD-L1 treatment. Cancer Immunol Res; 5(7); 560-70.",

author = "Jing Liao and Yan Luan and Zhenhua Ren and Xiaojuan Liu and Diyuan Xue and Hairong Xu and Zhichen Sun and Kaiting Yang and Hua Peng and Fu, {Yang Xin}",

note = "Funding Information: This work was supported by National Natural Science Foundation of China grant (No. 81172814) to H. Peng (No 881202328) to Y. Luan, Key deployment project from Chinese Academy of Sciences (No. KFZD-SW-205) to H. Peng, Ministry of Science and Technology of China grant (No. 2016YFC1303400 and No. 2011DFA31250) to Y.-X. Fu, and National Science and Technology Major Project of China grant (No. 2012ZX10001006) to H. Peng. This research was in part supported by the U.S. National Institutes of Health grants CA141975 to Y.-X. Fu. Publisher Copyright: {\textcopyright} 2017 American Association for Cancer Research.",

year = "2017",

month = jul,

doi = "10.1158/2326-6066.CIR-16-0221",

language = "English (US)",

volume = "5",

pages = "560--570",

journal = "Cancer immunology research",

issn = "2326-6066",

publisher = "American Association for Cancer Research Inc.",

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TY - JOUR

T1 - Converting lymphoma cells into potent antigen-presenting cells for interferon-induced tumor regression

AU - Liao, Jing

AU - Luan, Yan

AU - Ren, Zhenhua

AU - Liu, Xiaojuan

AU - Xue, Diyuan

AU - Xu, Hairong

AU - Sun, Zhichen

AU - Yang, Kaiting

AU - Peng, Hua

AU - Fu, Yang Xin

N1 - Funding Information: This work was supported by National Natural Science Foundation of China grant (No. 81172814) to H. Peng (No 881202328) to Y. Luan, Key deployment project from Chinese Academy of Sciences (No. KFZD-SW-205) to H. Peng, Ministry of Science and Technology of China grant (No. 2016YFC1303400 and No. 2011DFA31250) to Y.-X. Fu, and National Science and Technology Major Project of China grant (No. 2012ZX10001006) to H. Peng. This research was in part supported by the U.S. National Institutes of Health grants CA141975 to Y.-X. Fu. Publisher Copyright: © 2017 American Association for Cancer Research.

PY - 2017/7

Y1 - 2017/7

N2 - Anti-hCD20 is a therapeutic mAb that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-α (IFNα) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)- associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNα (anti-CD20-IFNα) depended on existing tumor-infiltrating CD8+ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APC) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Anti-CD20-IFNα also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti-CD20-IFNα eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8+ T cells and synergizing with anti-PD-L1 treatment. Cancer Immunol Res; 5(7); 560-70.

AB - Anti-hCD20 is a therapeutic mAb that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-α (IFNα) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)- associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNα (anti-CD20-IFNα) depended on existing tumor-infiltrating CD8+ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APC) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Anti-CD20-IFNα also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti-CD20-IFNα eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8+ T cells and synergizing with anti-PD-L1 treatment. Cancer Immunol Res; 5(7); 560-70.

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U2 - 10.1158/2326-6066.CIR-16-0221

DO - 10.1158/2326-6066.CIR-16-0221

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AN - SCOPUS:85021927694

SN - 2326-6066

VL - 5

SP - 560

EP - 570

JO - Cancer immunology research

JF - Cancer immunology research

IS - 7

ER -

Converting lymphoma cells into potent antigen-presenting cells for interferon-induced tumor regression

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