Journal of Vaccine Research 2024, Vol.14, No.5, 255-268 http://medscipublisher.com/index.php/jvr 256 2 Mechanisms of Cancer Vaccines in Breast Cancer 2.1 Antigen presentation and T-cell activation Cancer vaccines aim to stimulate the immune system to recognize and attack cancer cells by presenting tumor-associated antigens (TAAs) to T cells. The process begins with the uptake of TAAs by antigen-presenting cells (APCs), such as dendritic cells (DCs). These APCs process the antigens and present them on their surface via major histocompatibility complex (MHC) molecules. For effective T-cell activation, the antigens must be cross-presented by DCs to CD8+ T cells, which are crucial for cytotoxic responses against tumor cells. The stimulator of interferon genes (STING) pathway has been identified as a key player in enhancing antigen presentation. Activation of the STING pathway in DCs leads to the production of type I interferons and other cytokines, which enhance the cross-presentation of antigens and the activation of CD8+ T cells (Shae et al., 2020). Additionally, the use of adjuvants such as Toll-like receptor (TLR) agonists can further enhance the activation and maturation of DCs, leading to more effective T-cell priming. Tumors, however, have developed mechanisms to evade immune recognition, such as downregulating antigen presentation machinery or altering the antigen repertoire presented on their surface. These evasion strategies can significantly impair the effectiveness of cancer vaccines. Therefore, understanding and overcoming these mechanisms is crucial for the development of more effective cancer vaccines. 2.2 Role of immune memory The generation of long-term immune memory is a critical goal of cancer vaccination, as it ensures sustained surveillance and rapid response to tumor recurrence. Memory T cells, particularly memory CD8+T cells, play a pivotal role in this process. These cells can persist for extended periods and quickly expand upon re-exposure to the antigen, providing a robust and rapid immune response. Interleukin-7 (IL-7) has been identified as a key cytokine in the maintenance and survival of memory T cells. IL-7 promotes the homeostatic proliferation of memory T cells and enhances their longevity, making it a promising adjuvant for cancer vaccines. Additionally, the bone marrow has been recognized as a critical niche for the survival of memory T cells, providing a supportive environment that helps maintain their long-term persistence. Recent studies have shown that cancer vaccines can induce durable memory T cell responses. For instance, a DNA vaccine targeting Fos-related antigen 1 (Fra-1) and coexpressing IL-18 was found to induce long-lived T memory cells capable of eradicating established tumors upon re-challenge . These findings highlight the potential of cancer vaccines to provide long-term protection against tumor recurrence. 2.3 Boosting immune responses Boosting immune responses is essential for enhancing the efficacy of cancer vaccines. This can be achieved through various strategies, including the use of adjuvants, combination therapies, and heterologous boosting. Adjuvants such as TLR agonists, cytokines, and checkpoint inhibitors can enhance the activation and expansion of T cells, leading to more robust immune responses. Heterologous boosting, which involves using different vaccine platforms to deliver the same antigen, has been shown to enhance immune responses. For example, a study demonstrated that heterologous vaccination with different HER2-LAMP targeted vectors significantly augmented HER2-specific T and B cell responses, leading to more effective anti-tumor immunity (Marek et al., 2022). This approach can overcome the limitations of homologous boosting, where repeated use of the same vaccine platform may lead to diminished responses due to immune tolerance or vector-specific immunity. Combination therapies that include cancer vaccines and immune checkpoint inhibitors have also shown promise. These combinations can enhance the overall immune response by simultaneously promoting T cell activation and preventing immune suppression. For instance, the co-delivery of peptide neoantigens and STING agonists in a nanovaccine platform significantly enhanced CD8+T cell responses, when combined with checkpoint blockade, led to complete tumor rejection in murine models. In summary, boosting immune responses through adjuvants, heterologous boosting, combination therapies is crucial for the success of cancer vaccines in breast cancer. These strategies can enhance the activation, expansion, and memory formation of tumor-specific T cells, leading to more effective and durable anti-tumor immunity.
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