Journal of Vaccine Research 2024, Vol.14, No.5, 255-268 http://medscipublisher.com/index.php/jvr 264 promise. ICIs can reinvigorate exhausted T cells and enhance the durability of the immune response. Studies have indicated that combining cancer vaccines with ICIs can sustain and even boost the antitumor immune response, thereby mitigating the effects of waning immunity (Burg et al., 2016). Therefore, ongoing research is focused on optimizing vaccine formulations and exploring combination strategies to sustain long-term immunity in breast cancer patients. 7.2 Immunosenescence Immunosenescence, the gradual deterioration of the immune system associated with aging, poses a significant challenge in sustaining long-term immunity in breast cancer patients. As the immune system ages, there is a decline in the production of naive T cells and an accumulation of memory T cells, which can lead to a reduced ability to respond to new antigens, including those presented by cancer vaccines. This age-related decline in immune function can compromise the efficacy of cancer vaccines in elderly breast cancer patients, who represent a substantial proportion of the patient population. Several studies have highlighted the impact of immunosenescence on cancer immunotherapy. For instance, research has shown that elderly patients have lower levels of naive T cells and higher levels of senescent T cells, which can impair the generation of robust and long-lasting immune responses. Additionally, the presence of age-related chronic inflammation, or "inflammaging," can further exacerbate immune dysfunction and contribute to an immunosuppressive TME. Despite these challenges, there is evidence that elderly patients can still benefit from immunotherapy. Clinical experience with immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 antibodies, has shown that advanced age does not necessarily result in poorer responses or greater toxicity. This suggests that with appropriate strategies, it is possible to overcome the effects of immunosenescence. To enhance the efficacy of cancer vaccines in the elderly, researchers are exploring various approaches, including the use of adjuvants that can boost immune responses, the development of vaccines targeting multiple antigens, and the combination of vaccines with other immunotherapies (Burg et al., 2016). These strategies aim to counteract the effects of immunosenescence and improve the long-term immunological outcomes for elderly breast cancer patients. 7.3 Overcoming immune suppression Overcoming immune suppression is a critical challenge in sustaining long-term immunity in breast cancer patients receiving cancer vaccines. The TME is often characterized by various immunosuppressive mechanisms that can inhibit the effectiveness of cancer vaccines. These mechanisms include the presence of Tregs, MDSCs, and immunosuppressive cytokines, all of which can dampen the antitumor immune response. One approach to overcoming immune suppression is the use of combination therapies that target multiple aspects of the immune response. For example, the NANT Cancer Vaccine (NCV) combines low-dose chemotherapy, radiotherapy, and multifaceted immunotherapy to reverse the immunosuppressive TME, induce immunogenic tumor cell death, and reengage NK and T-cell responses . This coordinated approach has shown promise in early clinical trials, suggesting that it is possible to overcome immune suppression and achieve sustained antitumor immunity. Another strategy involves the use of immune checkpoint inhibitors to block inhibitory signals and enhance T-cell activation. Checkpoint inhibitors, such as anti-PD-1/PD-L1 and anti-CTLA-4 antibodies, have been shown to reinvigorate exhausted T cells and improve the efficacy of cancer vaccines (Burg et al., 2016). By blocking the inhibitory pathways, these agents can enhance the immune response and help maintain long-term immunity. Additionally, targeting specific components of the TME, such as Tregs and MDSCs, can also help overcome immune suppression. Agents that deplete Tregs or inhibit their function, as well as those that target MDSCs, are being investigated to enhance the effectiveness of cancer vaccines. These approaches aim to create a more favorable immune environment that supports sustained antitumor responses. In conclusion, overcoming immune suppression is essential for sustaining long-term immunity in breast cancer patients receiving cancer vaccines. Combination therapies, immune checkpoint inhibitors, and targeted approaches to modulate the TME are
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