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Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance


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Title: Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance
Authors: Muraoka, Daisuke / Seo, Naohiro / Hayashi, Tae / Tahara, Yoshiro / Fujii, Keisuke / Tawara, Isao / Miyahara, Yoshihiro / Okamori, Kana / Yagita, Hideo / Imoto, Seiya / Yamaguchi, Rui / Komura, Mitsuhiro / Miyano, Satoru / Goto, Masahiro / Sawada, Shin-ichi / Asai, Akira / Ikeda, Hiroaki / Akiyoshi, Kazunari / Harada, Naozumi / Shiku, Hiroshi
Issue Date: 1-Mar-2019
Publisher: American Society for Clinical Investigation
Citation: The Journal of clinical investigation, 129(3), pp.1278-1294; 2019
Abstract: Immune checkpoint inhibitors and adoptive transfer of gene-engineered T cells have emerged as novel therapeutic modalities for hard-to-treat solid tumors; however, many patients are refractory to these immunotherapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. By comparing the tumor microenvironment of checkpoint inhibition-sensitive and -resistant murine solid tumors, we observed that the resistant tumors had low immunogenicity. We identified antigen presentation by CD11b+F4/80+ tumor-associated macrophages (TAMs) as a key factor correlated with immune resistance. In the resistant tumors, TAMs remained inactive and did not exert antigen-presenting activity. Targeted delivery of a long peptide antigen to TAMs by using a nano-sized hydrogel (nanogel) in the presence of a TLR agonist activated TAMs, induced their antigen-presenting activity, and thereby transformed the resistant tumors into tumors sensitive to adaptive immune responses such as adoptive transfer of tumor-specific T cell receptor-engineered T cells. These results indicate that the status and function of TAMs have a significant impact on tumor immune sensitivity and that manipulation of TAM functions would be an effective approach for improving the efficacy of immunotherapies.
Keywords: Cancer immunotherapy / Immunology
URI: http://hdl.handle.net/10069/38899
ISSN: 00219738
DOI: 10.1172/JCI97642
Rights: © 2019, American Society for Clinical Investigation.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/38899

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