Overcoming cancer-associated fibroblast-induced immunosuppression by anti-interleukin-6 receptor antibody

• DOI: 10.1007/s00262-023-03378-7
• Publication Date: 2023-02-11T00:14:37Z
• Authors: Noriyuki Nishiwaki; Kazuhiro Noma; Toshiaki Ohara; Tomoyoshi Kunitomo; Kento Kawasaki; Masaaki Akai; Teruki Kobayashi; Toru Narusaka; Hajime Kashima; Hiroaki Sato; Satoshi Komoto; Takuya Kato; Naoaki Maeda; Satoru Kikuchi; Shunsuke Tanabe; Hiroshi Tazawa; Yasuhiro Shirakawa; Toshiyoshi Fujiwara
• Keywords: Immunosuppression; Tumor progression; Cancer-Associated Fibroblasts

Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play central role in progression. Previously, we reported that CAFs might induce immunosuppression via interleukin-6 (IL-6) promote progression by blocking local IL-6 with neutralizing antibody. Here, explore whether an anti-IL-6 receptor antibody could be used as systemic therapy to treat cancer, further investigate mechanisms which induces immunosuppression. In clinical samples, expression was significantly correlated α-smooth muscle actin expression, high cases showed Multivariate analysis independent prognostic factor. vitro, contributed cell proliferation differentiation into CAFs. Moreover, increased hypoxia-inducible factor 1α (HIF1α) induced enhancing glucose uptake cancer cells competing for immune cells. MR16-1, rodent analog antibody, overcame CAF-induced suppressed immunocompetent murine models regulating HIF1α activation vivo. The systemically employed overcome improve patient survival various cancers. Furthermore, suggested activation.