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J. Immunother. Cancer, 14 February 2025;13:e010371 | https://doi.org/10.1136/jitc-2024-010371
Boosting tumor homing of endogenous natural killer cells via therapeutic secretomes of chemically primed natural killer cells
Seohyun Cho, Seung Hee Choi , Eunchong Maeng, Hail Park, Ki Seo Ryu, Kyung-Soon Park
Division of life science, Department of Biomedical Science, CHA University, Seongnam-si, Korea (the Republic of)
SC and SHC contributed equally.
Correspondence to professor Kyung-Soon Park
Division of life science, Department of Biomedical Science, CHA University, Seongnam-si, Korea (the Republic of)
SC and SHC contributed equally.
Correspondence to professor Kyung-Soon Park
Abstract
Background Natural killer (NK) cells play a critical role in modulating immune responses by secreting soluble factors, including chemotactic cytokines. Our previous study demonstrated the potent antitumor activity of Chem_NK, referring to NK cells chemically primed with 25 kDa branched polyethyleneimine. However, the potential of Chem_NK secretomes to educate other NK cells and enhance their tumor-homing ability remains unexplored.
Methods The effects of Chem_NK conditioned media (Chem CM) on NK cells were evaluated in vitro by examining chemokine receptor expression and migration toward cancer cells. In vivo, the impact of Chem_NK and Chem CM on endogenous NK cell populations was assessed using xenograft and syngeneic mouse tumor models. Cytokine array and signaling analyses were performed to identify factors secreted by Chem_NK and their role in activating recipient NK cells.
Results Chem CM effectively educated NK cells in vitro, enhancing chemokine receptor expression and improving their migration toward cancer cells. In vivo, adoptively transferred Chem_NK increased endogenous NK cell populations within xenograft tumors. Furthermore, direct injection of Chem CM into a syngeneic mouse tumor model significantly promoted endogenous NK cell infiltration into tumors and suppressed lung metastasis. Cytokine analysis revealed that Chem_NK secreted high levels of cytokines, which activated ERK1/2 signaling in recipient NK cells, leading to upregulation of chemokine receptors.
Conclusions Chem_NK secretomes effectively enhance the tumor-homing ability of NK cells and amplify antitumor efficacy by educating other NK cells. These findings offer novel insights into activated NK cell-mediated immune communication and highlight the therapeutic potential of NK cell-derived secretomes in cancer therapy.
Methods The effects of Chem_NK conditioned media (Chem CM) on NK cells were evaluated in vitro by examining chemokine receptor expression and migration toward cancer cells. In vivo, the impact of Chem_NK and Chem CM on endogenous NK cell populations was assessed using xenograft and syngeneic mouse tumor models. Cytokine array and signaling analyses were performed to identify factors secreted by Chem_NK and their role in activating recipient NK cells.
Results Chem CM effectively educated NK cells in vitro, enhancing chemokine receptor expression and improving their migration toward cancer cells. In vivo, adoptively transferred Chem_NK increased endogenous NK cell populations within xenograft tumors. Furthermore, direct injection of Chem CM into a syngeneic mouse tumor model significantly promoted endogenous NK cell infiltration into tumors and suppressed lung metastasis. Cytokine analysis revealed that Chem_NK secreted high levels of cytokines, which activated ERK1/2 signaling in recipient NK cells, leading to upregulation of chemokine receptors.
Conclusions Chem_NK secretomes effectively enhance the tumor-homing ability of NK cells and amplify antitumor efficacy by educating other NK cells. These findings offer novel insights into activated NK cell-mediated immune communication and highlight the therapeutic potential of NK cell-derived secretomes in cancer therapy.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-03-06)
- 국내 연구진
- 생명과학 > 면역학
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