Reversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts

Xin Li, Tuying Yong (), Zhaohan Wei, Nana Bie, Xiaoqiong Zhang, Guiting Zhan, Jianye Li, Jiaqi Qin, Jingjing Yu, Bixiang Zhang, Lu Gan () and Xiangliang Yang ()
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Xin Li: Huazhong University of Science and Technology
Tuying Yong: Huazhong University of Science and Technology
Zhaohan Wei: Huazhong University of Science and Technology
Nana Bie: Huazhong University of Science and Technology
Xiaoqiong Zhang: Huazhong University of Science and Technology
Guiting Zhan: Huazhong University of Science and Technology
Jianye Li: Huazhong University of Science and Technology
Jiaqi Qin: Huazhong University of Science and Technology
Jingjing Yu: Huazhong University of Science and Technology
Bixiang Zhang: Huazhong University of Science and Technology
Lu Gan: Huazhong University of Science and Technology
Xiangliang Yang: Huazhong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Insufficient tumor accumulation and distribution of photosensitizers as well as low antitumor immunity severely restrict the therapeutic efficacy of photothermal therapy (PTT). Cancer-associated fibroblasts (CAFs) play a key role in tumor extracellular matrix (ECM) remodeling and immune evasion. Reshaping tumor microenvironment via CAF regulation might provide a potential approach for complete tumor elimination in combination with PTT. Here, tumor cell-derived microparticles co-delivering calcipotriol and Indocyanine green (Cal/ICG@MPs) are developed to modulate CAFs for improved PTT efficacy. Cal/ICG@MPs efficiently target tumor tissues and regulate CAFs to reduce tumor ECM, resulting in enhanced tumor accumulation and penetration of ICG to generate strong PTT efficacy and activate CD8+ T cell-mediated antitumor immunity. In addition, Cal/ICG@MPs-triggered CAF regulation enhances tumor infiltration of CD8+ T cells and ameliorates CAF-induced antigen-mediated activation-induced cell death of tumor-specific CD8+ T cells in response to PTT, eliciting long-term antitumor immune memory to inhibit tumor recurrence and metastasis. Our results support Cal/ICG@MPs as a promising drug to improve PTT efficacy in cancer treatment.

Date: 2022
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DOI: 10.1038/s41467-022-30306-7

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