Fig. 7

A Key elements and processes of an effective cancer vaccine. a The tumor antigen presentation process involves several steps. Initially, APCs such as DCs encounter antigens at the injection site or have antigens externally loaded onto them before injection, as in the case of DC vaccines. Antigen-loaded APCs then travel through the lymphatic system to the draining lymph nodes, where T cell activation primarily takes place. In the lymph node, mature DCs present tumor-derived peptides on MHC class I and II molecules to CD8 + and CD4 + T cells, both of naïve and memory types. The development of tumor-specific T cell responses is facilitated by delivering a costimulatory "signal 2" to T cells through interactions like CD80-CD28, CD86-CD28, CD70-CD27, and CD40-CD40 ligand (CD40L). Costimulation is enhanced by IL-12 and type I interferons (IFNs) produced by DCs. These interactions collectively support the generation and expansion of activated tumor-specific CD4 + and CD8 + T cell populations. CD4 + and CD8 + T cells migrate to the tumor site, and upon recognizing their specific antigens, they can destroy tumor cells through cytotoxicity and effector cytokine production, such as IFNγ and tumor necrosis factor (TNF). Consequently, lysed tumor cells release tumor antigens, which can be captured, processed, and presented by APCs to induce polyclonal T cell responses, thus increasing the antigenic variety of the anti-tumor immune response and leading to epitope spreading. b Cancer vaccines consist of four main components: tumor antigens, formulations, immune adjuvants, and delivery vehicles. Abbreviations: CpG ODN, CpG oligodeoxynucleotide; GM-CSF, granulocyte–macrophage colony-stimulating factor; MPL, monophosphoryl lipid A; poly-ICLC, polyinosinic–polycytidylic acid with polylysine and carboxymethylcellulose; STING, stimulator of interferon genes protein; TCR, T cell receptor; TLR, Toll-like receptor. Reprinted from [241] with permission from Springer Nature. B Key factors in the efficacy of directly injected mRNA vaccines. The effectiveness of an injected mRNA vaccine depends on several factors: the amount of antigen expression in professional APCs, which is affected by the carrier's efficiency, the presence of PAMPs such as double-stranded RNA (dsRNA) or unmodified nucleosides, and the optimization of the RNA sequence (including codon usage, G:C content, and 5' and 3' UTRs); the maturation and migration of DCs to secondary lymphoid tissues, which is enhanced by PAMPs; and the vaccine's capacity to stimulate strong T follicular helper (TFH) cell and germinal center (GC) B cell responses, an aspect that is not yet well-understood. An intradermal injection is provided as an illustration. EC refers to extracellular. Reprinted from [126] with permission from Springer Nature