School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Cancer Immunol Immunother. 2021 Nov;70(11):3217-3233. doi: 10.1007/s00262-021-02917-4. Epub 2021 Apr 5.
Photodynamic therapy (PDT) is a clinically approved treatment for various types of cancer. Besides killing the tumor cells directly, PDT has also been reported to trigger anti-tumor immunity. In our previous study, BAM-SiPc-based PDT was shown to induce immunogenic cell death on CT26 murine colon tumor cells in vitro. Using the BALB/c mouse animal model and a vascular-PDT (VPDT) approach, it could also eradicate tumor in ∼ 70% of tumor-bearing mice and elicit an anti-tumor immune response. In the present study, the serum obtained from the VPDT-cured mice was studied and found to possess various immunomodulatory properties. In in vitro studies, it stimulated cytokine secretions of IL-6 and C-X-C motif chemokine ligands 1-3 in CT26 cells through the NF-κB and MAPK pathways. The complement protein C5a boosted in the serum was shown to be involved in the process. The serum also induced calreticulin exposure on CT26 cells and activated dendritic cells. It contained CT26-targeting antibodies which, through the Fc region, induced macrophage engulfment of the tumor cells. In in vivo studies, inoculation of the serum-treated CT26 cells to mice demonstrated a retarded tumor growth with leukocytes, particularly T cells, attracted to the tumor site. In addition, the VPDT-cured mice showed different degrees of resistance against challenge of other types of murine tumor cells, for example, the breast tumor 4T1 and EMT6 cells.
光动力疗法（PDT）是一种临床认可的治疗各种类型癌症的方法。除了直接杀死肿瘤细胞外，PDT 还被报道能触发抗肿瘤免疫。在我们之前的研究中，基于 BAM-SiPc 的 PDT 被证明能在体外诱导 CT26 小鼠结肠肿瘤细胞发生免疫原性细胞死亡。使用 BALB/c 小鼠动物模型和血管 PDT（VPDT）方法，它还能在约 70%的荷瘤小鼠中根除肿瘤，并引发抗肿瘤免疫反应。在本研究中，研究了来自 VPDT 治愈小鼠的血清，发现其具有多种免疫调节特性。在体外研究中，它通过 NF-κB 和 MAPK 途径刺激 CT26 细胞中细胞因子 IL-6 和 C-X-C 基序趋化因子配体 1-3 的分泌。血清中增加的补体蛋白 C5a 被证明参与了这一过程。该血清还诱导 CT26 细胞表面钙网蛋白的暴露，并激活树突状细胞。它含有针对 CT26 的抗体，通过 Fc 区域诱导巨噬细胞吞噬肿瘤细胞。在体内研究中，将经血清处理的 CT26 细胞接种到小鼠中，证明肿瘤生长缓慢，白细胞，特别是 T 细胞，被吸引到肿瘤部位。此外，VPDT 治愈的小鼠对其他类型的小鼠肿瘤细胞（例如乳腺癌 4T1 和 EMT6 细胞）的攻击表现出不同程度的抗性。
