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M1 Macrophage-Derived Nanovesicles Potentiate the Anticancer Efficacy of Immune Checkpoint Inhibitors

Yeon Woong ChooSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaMikyung KangInterdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of KoreaHan Young KimSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaJin HanSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaSeokyung KangSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaJu‐Ro LeeSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaGun‐Jae JeongSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaSung Pil KwonSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaSeuk Young SongSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaSeokhyeong GoInterdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of KoreaMungyo JungSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaJihye HongInterdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of KoreaByung‐Soo KimInstitute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea

2018en

ABI

Аннотация

Cancer immunotherapy modulates immune cells to induce antitumor immune responses. Tumors employ immune checkpoints to evade immune cell attacks. Immune checkpoint inhibitors such as anti-PD-L1 antibody (aPD-L1), which is being used clinically for cancer treatments, can block immune checkpoints so that the immune system can attack tumors. However, immune checkpoint inhibitor therapy may be hampered by polarization of macrophages within the tumor microenvironment (TME) into M2 tumor-associated macrophages (TAMs), which suppress antitumor immune responses and promote tumor growth by releasing anti-inflammatory cytokines and angiogenic factors. In this study, we used exosome-mimetic nanovesicles derived from M1 macrophages (M1NVs) to repolarize M2 TAMs to M1 macrophages that release pro-inflammatory cytokines and induce antitumor immune responses and investigated whether the macrophage repolarization can potentiate the anticancer efficacy of aPD-L1. M1NV treatment induced successful polarization of M2 macrophages to M1 macrophages in vitro and in vivo. Intravenous injection of M1NVs into tumor-bearing mice suppressed tumor growth. Importantly, injection of a combination of M1NVs and aPD-L1 further reduced the tumor size, compared to the injection of either M1NVs or aPD-L1 alone. Thus, our study indicates that M1NV injection can repolarize M2 TAMs to M1 macrophages and potentiate antitumor efficacy of the checkpoint inhibitor therapy.

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DOI: 10.1021/acsnano.8b02446

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