常规 I 型树突状细胞中的趋化因子-趋化因子受体网络：激发和增强抗癌免疫的机会

Type I conventional dendritic cells (cDC1s) are key drivers of antitumor immunity. In human cancers, their presence correlates with better prognosis and survival benefits. In preclinical mouse tumor models, cDC1s are indispensable for successful T-cell-mediated tumor killing and therapeutic response to immune checkpoint blockade therapies. The essential role of cDC1s in antitumor immunity stems from their ability to uptake tumor-derived antigens and traffic them to the tumor-draining lymph node (tdLN) for T-cell priming. At the tdLN, cDC1s present tumor antigens to naïve CD8 + T cells and polarize them into tumor-specific cytotoxic T cells that eventually kill the tumor cells. Within the tumor, cDC1s secrete the chemokines CXCL9 and CXCL10 that recruit CXCR3 + effector natural killer and T cells and thereby sustain a local cytotoxic T-cell response.

The trafficking and migration of cDC1s to the tumor and tdLNs are largely mediated by a chemokine-chemokine receptor network linking cDC1s to their interacting immune cell partners. In this review, we discuss 2 key chemokine ligand-receptor pairs, C-C chemokine ligand 5-C-C chemokine receptor 5 and X-C chemokine ligand 1-X-C chemokine receptor 1, that play essential roles in directing cDC1 migration to the tumor.

Strategies that harness these cDC1-recruiting chemokine systems offer invaluable therapeutic prospects for enhancing current vaccine design and cancer immunotherapies. SIGNIFICANCE STATEMENT: The lack of type I conventional dendritic cells (cDC1s) in tumors represents a major roadblock for current cancer immunotherapies.

Here, we highlight 2 chemokines, C-C chemokine ligand 5 and X-C chemokine ligand 1, that are critical for recruiting cDC1s to the tumor microenvironment, where they uptake tumor antigens and cross-present antigens to T cells following migration to the lymph nodes.

We further discuss recent advances and limitations in current dendritic cell vaccine design and cancer adjuvant therapies, and propose new strategies to enhance cDC1 recruitment into tumors.