Selective depletion of polymorphonuclear myeloid derived suppressor cells in tumor beds with near infrared photoimmunotherapy enhances host immune response.
Selective depletion of polymorphonuclear myeloid derived suppressor cells in tumor beds with near infrared photoimmunotherapy enhances host immune response.
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DOI：
10.1080/2162402x.2022.2152248
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发表时间：
2022
期刊：
影响因子：
7.2
通讯作者：
Kobayashi, Hisataka
中科院分区：
文献类型：
--
作者：
Kato, Takuya;Fukushima, Hiroshi;Furusawa, Aki;Okada, Ryuhei;Wakiyama, Hiroaki;Furumoto, Hideyuki;Okuyama, Shuhei;Takao, Seiichiro;Choyke, Peter L.;Kobayashi, Hisataka
关键词：
免疫系统被认为是调节癌症发生、进展和转移的重要因素。骨髓源性抑制细胞 (MDSC) 是一种主要的免疫抑制细胞类型，通过干扰 T 细胞活化、促进效应 T 细胞凋亡和诱导调节性 T 细胞扩增。因此，减少或消除 MDSC 已成为一些全身免疫疗法的目标。然而，通过系统性地减少 MDSC，可能会出现不需要的副作用。近红外光免疫疗法（NIR-PIT）是一种新开发的治疗方法，可选择性杀死目标细胞而不损害邻近的正常细胞。本研究的目的是评估 MDSC 导向的 NIR-PIT 在同基因小鼠模型中利用抗 Ly6G 抗体特异性破坏肿瘤微环境 (TME) 中的多形核 (PMN)-MDSC 的抗肿瘤功效。 Ly6G 靶向的 NIR-PIT 可选择性消除肿瘤内的 PMN-MDSC。在三种治疗的肿瘤模型中，肿瘤生长受到显着抑制并延长了生存期。在 NIR-PIT 后的早期阶段，瘤内组织和肿瘤引流淋巴结中的树突状细胞成熟/激活和 CD8+ T 细胞激活均增强，并且 NK 细胞表现出细胞毒性分子表达增加。 NIR-PIT 后，宿主免疫在 TME 中保持激活至少一周。在双侧肿瘤模型中观察到远隔效应。此外，靶向癌细胞的 NIR-PIT 和 PMN-MDSC 的组合产生了协同效应，并表现出高度激活的宿主肿瘤免疫。总之，我们证明通过 NIR-PIT 选择性局部 PMN-MDSC 耗竭可能是一种有前途的新型癌症免疫疗法。
The immune system is recognized as an important factor in regulating the development, progression, and metastasis of cancer. Myeloid-derived suppressor cells (MDSCs) are a major immune-suppressive cell type by interfering with T cell activation, promoting effector T cell apoptosis, and inducing regulatory T cell expansion. Consequently, reducing or eliminating MDSCs has become a goal of some systemic immunotherapies. However, by systemically reducing MDSCs, unwanted side effects can occur. Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed treatment that selectively kills targeted cells without damaging adjacent normal cells. The aim of this study is to evaluate the antitumor efficacy of MDSC-directed NIR-PIT utilizing anti-Ly6G antibodies to specifically destroy polymorphonuclear (PMN)-MDSCs in the tumor microenvironment (TME) in syngeneic mouse models. PMN-MDSCs were selectively eliminated within tumors by Ly6G-targeted NIR-PIT. There was significant tumor growth suppression and prolonged survival in three treated tumor models. In the early phase after NIR-PIT, dendritic cell maturation/activation and CD8+ T cell activation were enhanced in both intratumoral tissues and tumor-draining lymph nodes, and NK cells demonstrated increased expression of cytotoxic molecules. Host immunity remained activated in the TME for at least one week after NIR-PIT. Abscopal effects in bilateral tumor models were observed. Furthermore, the combination of NIR-PIT targeting cancer cells and PMN-MDSCs yielded synergistic effects and demonstrated highly activated host tumor immunity. In conclusion, we demonstrated that selective local PMN-MDSCs depletion by NIR-PIT could be a promising new cancer immunotherapy.