Temperature sensitive liposome based cancer nanomedicine enables tumour lymph node immune microenvironment remodelling

Shunli Fu, Lili Chang, Shujun Liu, Tong Gao, Xiao Sang, Zipeng Zhang, Weiwei Mu, Xiaoqing Liu, Shuang Liang, Han Yang, Huizhen Yang, Qingping Ma, Yongjun Liu () and Na Zhang ()
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Shunli Fu: Shandong University
Lili Chang: Shandong University
Shujun Liu: Shandong University
Tong Gao: Shandong University
Xiao Sang: Shandong University
Zipeng Zhang: Shandong University
Weiwei Mu: Shandong University
Xiaoqing Liu: Shandong University
Shuang Liang: Shandong University
Han Yang: Shandong University
Huizhen Yang: Shandong University
Qingping Ma: Shandong University
Yongjun Liu: Shandong University
Na Zhang: Shandong University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Targeting tumour immunosuppressive microenvironment is a crucial strategy in immunotherapy. However, the critical role of the tumour lymph node (LN) immune microenvironment (TLIME) in the tumour immune homoeostasis is often ignored. Here, we present a nanoinducer, NIL-IM-Lip, that remodels the suppressed TLIME via simultaneously mobilizing T and NK cells. The temperature-sensitive NIL-IM-Lip is firstly delivered to tumours, then directed to the LNs following pH-sensitive shedding of NGR motif and MMP2-responsive release of IL-15. IR780 and 1-MT induces immunogenic cell death and suppress regulatory T cells simultaneously during photo-thermal stimulation. We demonstrate that combining NIL-IM-Lip with anti-PD-1 significantly enhances the effectiveness of T and NK cells, leading to greatly suppressed tumour growth in both hot and cold tumour models, with complete response in some instances. Our work thus highlights the critical role of TLIME in immunotherapy and provides proof of principle to combine LN targeting with immune checkpoint blockade in cancer immunotherapy.

Date: 2023
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DOI: 10.1038/s41467-023-38014-6

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