Autologous erythrocyte microparticles drive antitumour T cell immunity via haem-mediated dendritic cell activation
(1) Tang K (2) Liang Y (3) Sun W (4) Zheng X (5) Lu S (6) Chen Z (7) Yan Z (8) Liu S (9) Liu Y (10) Chen Y (11) Deng J (12) Zhang H (13) Ma J (14) Chen J (15) Zhou Y (16) Lv J (17) Huang B
Tang, Liang, Sun et al. developed a process to prepare haem-containing erythrocyte-derived microparticles (EMPs) from UV-irradiated erythrocytes as DC adjuvants. EMPs mixed with tumor cell lysates simultaneously activated and delivered antigen to DCs in vivo, providing CD8+ T cell-dependent prophylactic and therapeutic tumor control and enhanced survival. EMPs functioned by haem binding the nuclear receptor REV-ERBα, thereby inhibiting PPARγ transcription and driving DC activation. Human erythrocyte-derived EMPs were active in stimulating human DC maturation, and demonstrated in vivo activity in a humanized model.
Contributed by Ed Fritsch
(1) Tang K (2) Liang Y (3) Sun W (4) Zheng X (5) Lu S (6) Chen Z (7) Yan Z (8) Liu S (9) Liu Y (10) Chen Y (11) Deng J (12) Zhang H (13) Ma J (14) Chen J (15) Zhou Y (16) Lv J (17) Huang B
Tang, Liang, Sun et al. developed a process to prepare haem-containing erythrocyte-derived microparticles (EMPs) from UV-irradiated erythrocytes as DC adjuvants. EMPs mixed with tumor cell lysates simultaneously activated and delivered antigen to DCs in vivo, providing CD8+ T cell-dependent prophylactic and therapeutic tumor control and enhanced survival. EMPs functioned by haem binding the nuclear receptor REV-ERBα, thereby inhibiting PPARγ transcription and driving DC activation. Human erythrocyte-derived EMPs were active in stimulating human DC maturation, and demonstrated in vivo activity in a humanized model.
Contributed by Ed Fritsch
ABSTRACT: Current vaccine adjuvants, such as aluminum salts and emulsions, are limited by weak induction of cytotoxic T cell immunity and restricted ability to promote T helper type 1 responses, highlighting the need for safer and more effective alternatives. Here we show that microparticles generated from erythrocytes by controlled ultraviolet irradiation function as potent T helper type 1-skewing adjuvants that enhance tumour antigen-specific cytotoxic T cell responses in vitro and in multiple mouse tumour models. Following uptake by dendritic cells, these microparticles traffic to lysosomes and deliver haem cargo that is subsequently transported to the nucleus. Mechanistically, the particles elevate lysosomal pH, promoting lysosome movement towards the nucleus and enabling haem transfer, where haem activates REV-ERB_ and forms a co-repressor complex that suppresses peroxisome proliferator-activated receptor gamma, thereby relieving inhibition of dendritic cell maturation and antigen presentation. In vaccination settings, combining tumour antigens with erythrocyte-derived microparticles enhances cytotoxic T cell activation and suppresses tumour growth with minimal toxicity. These findings establish host-derived vesicles as a promising platform for next-generation cancer vaccine adjuvants.
Author Info:
(1) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ketang@hust.edu.cn. Department of Breast
and Thyroid Surgery, Union Hospital, Huazhong University of Science and Technology, Wuhan, China. ketang@hust.edu.cn. (2) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (3) School of Medicine, Xinxiang University, Xinxiang, China. (4) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (5) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (6) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (7) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (8) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (9) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (10) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (11) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (12) Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (13) Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (14) Department of Immunology and State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. (15) Department of Immunology and State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. (16) Department of Immunology and State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. (17) Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. tjhuangbo@hotmail.com. Department of Immunology and State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. tjhuangbo@hotmail.com.
Citation: Nat Biomed Eng 2026 Oct 23 Epub10/23/2026
