Dendritic cells instruct T cell anti-tumor immunity and immunotherapy response

Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells (APCs). They play pivotal roles in orchestrating innate and adaptive immune responses, particularly in cancer. In tumor-draining lymph nodes (tdLNs), de novo priming occurs, where DCs present antigens to naive T cells, activating them and initiating their clonal expansion. In the tumor microenvironment (TME), intratumoral DCs provide survival or co-stimulatory signals to shape T cell differentiation. However, the scarcity and dysfunctional states of DCs can greatly limit anti-tumor responses, and DCs can even be hijacked by tumor-related factors to promote tumor progression. Therefore, comprehensively understanding the anti- or pro-tumor activities of DCs is crucial. In this review, we discuss the ontogeny of DC lineages and the emerging complexity of intratumoral DCs states. Importantly, we emphasize the significant roles of DCs in priming and sustaining productive T cell anti-tumor immunity. In light of these findings, we also explore promising approaches for targeting DCs to boost anti-tumor immunity and overcome resistance to cancer immunotherapies. We propose that insights into the rational design of DC-based immunotherapeutic strategies against cancer hold immense, underexploited potential.