Journal of Vaccine Research 2024, Vol.14, No.4, 183-195 http://medscipublisher.com/index.php/jvr 184 Through this study, we hope to provide insights that will guide future research and development in the field of cancer immunotherapy. 2 Mechanisms of Action of Adjuvants 2.1 Immune system modulation Adjuvants modulate the immune system by targeting antigen-presenting cells (APCs) such as dendritic cells (DCs). This modulation is crucial for overcoming the immunosuppressive environment often associated with tumors. For instance, Toll-like receptor (TLR) agonists are commonly used adjuvants that activate DCs, leading to their maturation and enhanced ability to present antigens to T cells (Seya et al., 2015; Ho et al., 2018; Hernandez and Malek, 2022). The use of TLR2 and TLR3 agonists has shown promise in safely enhancing antitumor immunity by improving the cross-presentation of antigens and upregulating costimulatory molecules necessary for T-cell activation (Seya et al., 2015). Moreover, adjuvants can induce the production of cytokines and chemokines that support lymphocyte attraction and survival, further enhancing the immune response (Thorne et al., 2020). For example, the combination of STING agonists with TLR4 or TLR7/8 agonists has been shown to synergistically activate both murine and human APCs, leading to improved T-cell priming and antitumor responses (Figure 1) (Taylor et al., 2022). Figure 1 MuSyC-dose can optimize activation for multiple APCs in vitro (Adapted from Taylor et al., 2022) Image caption: (A) Corresponding dose-response curves for CDN (STING) and R848 (TLR7/8) for the activation of mBMDCs with the saturation range for each adjuvant in the red box. 20 µg/ml was chosen for CDN and 0.1 µg/ml was chosen for R848. (B) mBMDCs activated with R848, CDN, Max-dose (CDN of 20 µg/ml + R848 of 0.1 µg/ml), and MuSyC-dose (20 µg/ml + R848 of 0.01 µg/ml). The fold change gMFI normalized to the average no stim control of the activation markers are shown. (C) Murine bone marrow-derived macrophages (mBMDM) activation with the doses selected through the corresponding dose-response; (D) Human monocytic cell line (TH-P1) activation with appropriate doses; Figure 1 B is given in mean±SEM for two independent experiments. All other data are given in mean ± S.D. of three technical replicates. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001; one-way analysis of variance (ANOVA) for multiple comparisons. ns, not significant (Adapted from Taylor et al., 2022)
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