Neoantigen-based dendritic cell vaccines in lung cancer: overcoming immunosuppressive barriers for durable antitumor...

Cancer immunotherapies developed based on mechanisms of tumour immune evasion represent a major breakthrough in the history of cancer treatment, capable of reversing T-cell exhaustion induced by tumours through immune checkpoint blockade. However, the predominant focus on T cells as central players in antitumour immunity may have led to the oversight of the crucial role played by dendritic cells (DCs), which are essential for activating and directing T cells against tumour cells. DCs comprise a diverse group of antigen-presenting cells that play an indispensable role in initiating and regulating both innate and adaptive immune responses. Strategies aimed at modulating DC function to enhance cancer immunotherapy are therefore of critical importance. Beyond the development of novel immune checkpoint inhibitors, neoantigen-based DC vaccines represent a promising approach for developing personalised precision immunotherapies. Here, we review the molecular mechanisms underlying DC immunosuppression within the lung tumour microenvironment, how tumour-infiltrating DCs influence immunity and tolerance in the cancer setting, the mechanisms by which tumour-specific neoantigens elicit immune responses, the identification of neoantigens, and recent clinical advances in neoantigen-targeted vaccines for lung cancer. We also discuss recent progress in DC vaccine-based cancer immunotherapies from both preclinical studies and clinical trials.