BLOCKADE OF PD-1/PD-L1 ENHANCES APC FUNCTION OF FIBROCYTES
Afroj, Tania Tokushima University
Mitsuhashi, Atsushi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Ogino, Hirokazu Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Otsuka, Kenji Tokushima University Tokushima University Educator and Researcher Directory
Yoneda, Hiroto Tokushima University Tokushima University Educator and Researcher Directory
Nguyen, Na Thi Tokushima University
Koyama, Kazuya Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Sugimoto, Masamichi Chugai Pharmaceutical
Kondoh, Osamu Chugai Pharmaceutical
Nokihara, Hiroshi Tokushima University Tokushima University Educator and Researcher Directory
Thesis or Dissertation
Fibrocytes, a distinct population of collagen-producing, monocyte-derived cells, are involved in wound healing as well as fibrotic diseases. Recently, fibrocytes have been revealed to play a role in the tumor microenvironment, particularly under antiangiogenic therapy. In addition, combination cancer immunotherapy with immune checkpoint inhibitor and antiangiogenic agents have been developed for various cancers in the clinical setting, although the immunological background is not clear. In the current study, we aimed to determine the function of fibrocytes in tumor immunity induced by immune checkpoint inhibitor therapy. Human and murine fibrocytes were generated from PBMCs and lungs, respectively. The expression of costimulatory and inhibitory molecules on fibrocytes was examined by flow cytometry. The stimulation of CD8+ T cells by fibrocytes was examined in MLRs with a 3H-thymidine incorporation assay. Fibrocytes expressed CD80low and CD86high as a costimulatory molecule, and expressed PD-L1high, but not PD-L2, as a coinhibitory molecule.Without any stimulation, fibrocytes strongly enhanced the proliferation of CD8+ T cells in mice and humans. Treatment with anti-CD86 and -CD54 Abs inhibited the growth of CD8+ T cells induced by fibrocytes. Anti–PD-L1 Ab further enhanced the proliferation of CD8+ T cells, even in the OVA-specific MLR with OT-1Rag-/- mice. Importantly, fibrocytes derived from PBMCs of patients with lung adenocarcinoma or murine MC38 tumors augmented the proliferation of CD8+ T cells with PD-L1 blockade. These results suggest that fibrocytes infiltrating tumor sites may play a role in the antitumor immunity mediated by CD8+ T cells when the activity is further enhanced by PD-L1/PD-1 blockade.
The Journal of Immunology
The American Association of Immunologists, Inc.
Originally published in The Journal of Immunology. Tania Afroj, Atsushi Mitsuhashi, Hirokazu Ogino, Atsuro Saijo, Kenji Otsuka, Hiroto Yoneda, Makoto Tobiume, Na Thi Nguyen, Hisatsugu Goto, Kazuya Koyama, Masamichi Sugimoto, Osamu Kondoh, Hiroshi Nokihara and Yasuhiko Nishioka. 2021. Blockade of PD-1/PD-L1 Pathway Enhances the Antigen-Presenting Capacity of Fibrocytes. J. Immunol. Vol.206(6) pp1204-1214.
Copyright © 2021 by The American Association of Immunologists, Inc.
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|MEXT report number||
Doctor of Medical Science