Effects of immunogenic cell death-inducing chemotherapeutics on the immune cell activation and tertiary lymphoid structure formation in melanoma

作者：Hua Zhao, Yu Zhao, Siyuan Zhang, Zhe Wang, Wenwen Yu, Nan Dong, Xuena Yang, Xi‐Ying Zhang, Qian Sun, Xishan Hao, Xiubao Ren · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1302751 · 被引用次数：15 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Phagocytosis and Immune Regulation

Background The infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas. Methods Doxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining. Results Doxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8 + T cells and tissue-resident memory T cells (T RM ) and an increase in the secretion of interferon-γ, granzyme B, and perforin i...