Enhanced tumor control activities of anti-mPD-L1 antibody and antigen-presenting cell-like natural killer cell in an allograft model

• Published in: BMC cancer Vol. 24; no. 1; pp. 136 - 11
• Main Authors: Hung, Yi-Ping, Tu, Chia-Chun, Lai, Jiun-I, Yang, Muh-Hwa, Lee, Jan-Mou, Chao, Yee
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.01.2024; BioMed Central; BMC
• Subjects: Adoptive cell therapy; Allografts; Allografts - metabolism; Analysis; Animals; Antibodies; Antigen-presenting cells; Antigens; B7-H1 Antigen - metabolism; Care and treatment; CD4 antigen; CD8 antigen; Cell death; Cell Line, Tumor; Cell therapy; Colony-stimulating factor; Cytotoxicity; Dendritic Cells; Diagnosis; Female; Flow cytometry; Health aspects; Immune checkpoint inhibitor; Immune checkpoint inhibitors; Immune system; Immunotherapy; Interleukin 15; Killer cells; Killer Cells, Natural; Laboratory animals; Leukocyte migration; Leukocytes (granulocytic); Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Lymphoma; Metastases; Mice; Mice, Inbred C57BL; Monocytes; Natural killer cells; Neoplasms; NKDC; Non-Hodgkin's lymphomas; Patient outcomes; Peripheral blood; Reagents; Testing; Tumor antigens; Tumor Microenvironment; Tumors; Taiwan; United States > US; NKDC; Immune checkpoint inhibitor; Tumor microenvironment; Adoptive cell therapy; Immunotherapy
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-11889-4

Despite the utilization of immune checkpoint inhibitors (ICIs) in treating numerous types of cancers being approved, their efficacy in tumor control in the clinic is not satisfactory. Since adoptive cell therapy (ACT) can alter the tumor microenvironment, we hypothesized that ACT potentially synergized with ICI in tumor control and examined this hypothesis via a murine allograft model. Female C57BL/6 mice were stimulated with interleukin 15 and granulocyte monocyte-colony stimulating factor, followed by collecting their bone marrow cells for murine NKDC cultivation. Then, female C57BL/6 mice, inoculated with lymphoma cancer cell line E.G7-OVA, were administrated with murine NKDC cells, murine anti-program cell death ligand-1 antibody (α-mPD-L1), or both for 28 days. After 28 days of treatment, mice were sacrificed whose inoculated tumors, spleen, sentinel lymph nodes, and peripheral blood were collected to measure tumor size, lymphocyte infiltration, and change of immune cell profile. Combined treatment of NKDCs with α-mPD-L1 exhibited significantly stronger tumor control efficacy than treatment of NKDCs or α-mPD-L1 alone. NKDCs/α-mPD-L1 combination increased migration of dendritic cells, CD4, CD8 T cells, and activated CD8 T cells to the tumor-bedding site, and promoted endogenous tumor-specific cytotoxic T-cell response. The current study confirmed our hypothesis that combining NKDC ACT with ICI therapy can potentiate tumor control efficacy by manipulating the tumor microenvironment. This study provided a novel circumstance on tumor immunotherapy.