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Contribution of immune cells in synergistic anti-tumor effect of ablation and immunotherapy.

ABSTRACT: Thermal ablation results in the damage of tumor tissue, which leads to localized necrosis and incites a significant inflammatory response, accompanied by the infiltration of numerous immune cells. Nevertheless, depending solely on the singular approach of thermal ablation frequently is difficult in eliciting a robust anti-tumor response. Research suggests that integrating immune modulators into conventional ablation techniques has the potential to enhance the elicited immune response, finally initiating synergistic effect without significantly elevated risk profiles. This article comprehensively analyses the immunological effects resulting from post-ablation alone and its synergy with immunotherapies, and accentuates the heterogeneous alterations noted in immune cells across distinct malignancies. Collectively, the article delves into the theoretical framework and advancements in clinical trials concerning the combined thermal ablation and immunotherapy for treating malignant tumors.

SUBMITTER: He N

PROVIDER: S-EPMC10755586 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Contribution of immune cells in synergistic anti-tumor effect of ablation and immunotherapy.

He Ningning N Jiang Jingting J

Translational oncology 20231208

Thermal ablation results in the damage of tumor tissue, which leads to localized necrosis and incites a significant inflammatory response, accompanied by the infiltration of numerous immune cells. Nevertheless, depending solely on the singular approach of thermal ablation frequently is difficult in eliciting a robust anti-tumor response. Research suggests that integrating immune modulators into conventional ablation techniques has the potential to enhance the elicited immune response, finally in ...[more]

PMID: 38070356

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Project description:BackgroundImmune checkpoint blockades (ICBs) therapy showed limited efficacy in ovarian cancer management. Increasing evidence indicated that conventional and targeted therapies could affect tumor-associated immune responses and increase the effectiveness of immunotherapy. However, the effects of Niraparib, one of the poly (ADP) ribose polymerase (PARP) inhibitors, on the immune response remains unclear. Delineating the crosstalk between cytotoxic anticancer agents and cancer-associated immunity may lead to more efficient combinatorial strategies.MethodsProgrammed death ligand 1 (PD-L1) expression in human ovarian cancer cells after PARP inhibitors treatment was examined by western blotting (WB) and flow cytometry. The expression of poly ADP-ribose polymerase (PARP1), PD-L1, and CD8 in human ovarian cancer tissues was detected by immunohistochemistry(IHC). The effect of Niraparib and PD-L1 blockade in ovarian cancer progression was investigated in vivo. The changes of immune cells and cytokines in vitro and in vivo were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Changes of cGAS/STING signal pathway after Niraparib treatment were determined by WB, ELISA.ResultsNiraparib upregulated membrane PD-L1 and total PD-L1 expression in ovarian cancer cells and had a synergistic effect with PD-L1 blockade in vivo. In clinical patient samples, Niraparib augmented cytotoxic CD8+T cell proportion and function. In vivo and vitro, Niraparib can also increase the proportion of T cells and combined with PD-L1 blockade could further enhance the effect. Besides, Niraparib activated the cGAS-STING pathway, increasing the levels of cytokines such as CCL5 and CXCL10, which played a vital role in augmenting the infiltration and activation of cytotoxic T cells.ConclusionsNiraparib could modulate the immune response via the activation of the cGAS/STING pathway, and combination with PD-L1 blockade could further enhance the effect. These results provide a sound theoretical basis for clinical treatment.

Dataset Information

Contribution of immune cells in synergistic anti-tumor effect of ablation and immunotherapy.

Publications

Contribution of immune cells in synergistic anti-tumor effect of ablation and immunotherapy.

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