Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 234-253 http://medscipublisher.com/index.php/cge 240 For example, a study demonstrated that DCs loaded with colon cancer stem cell-derived antigens significantly suppressed tumor growth and extended survival in a mouse model of colorectal carcinoma (Fu et al., 2021). The complex crosstalk between CRC and DCs still need to be further unraveled (Subtil et al., 2021). Another promising approach involves in situ DC vaccines, which are designed to generate tumor-associated antigens (TAAs) directly within the tumor microenvironment. These vaccines use polymersomal nanoformulations that combine immunogenic cell death inducers and photosensitizers to enhance antigen presentation and stimulate a strong immune response (Yang et al., 2019). 4.3.3 Additional approaches and combination therapies In addition to peptide and DC vaccines, other innovative strategies are being explored to improve the efficacy of cancer vaccines. For instance, personalized cancer vaccines, which are tailored to the unique mutational landscape of an individual’s tumor, have shown promise in clinical trials. These vaccines harness next-generation sequencing and bioinformatics to identify and target neoantigens, which are specific to the cancer cells. Combination therapies that integrate cancer vaccines with other immunotherapies, such as immune checkpoint inhibitors, are also being investigated. This approach aims to overcome the immunosuppressive tumor microenvironment and enhance the overall anti-tumor response. Clinical trials have demonstrated that combining vaccines with agents like PD-1 inhibitors can significantly improve therapeutic outcomes (Azadi et al., 2021; Kim et al., 2021; Zhao et al., 2019). 4.4 Oncolytic viruses Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively infect and kill cancer cells while sparing normal tissues. These viruses can replicate within tumor cells, causing cell lysis and the release of tumor antigens, which can subsequently stimulate an anti-tumor immune response. One significant advantage of oncolytic viruses is their ability to convert "cold" tumors, which are poorly infiltrated by immune cells, into "hot" tumors, which are more amenable to immune system attack (Omole et al., 2022). Several oncolytic viruses have been studied for their potential in colon cancer therapy. For example, the oncolytic vaccinia virus has demonstrated the ability to rejuvenate the immune microenvironment in colon cancer by promoting the infiltration and activation of CD8+ T cells and dendritic cells within the tumor, enhancing the overall anti-tumor immunity (Lee et al., 2020). Additionally, combining oncolytic viruses with immune checkpoint inhibitors, such as anti-PD-1 antibodies, has shown synergistic effects, resulting in improved tumor control and prolonged survival in preclinical models (Shi et al., 2019). Oncolytic viruses can also be engineered to express therapeutic genes, such as cytokines or other immune-stimulatory molecules, further enhancing their anti-tumor effects. For instance, viruses expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) have been shown to boost local immune responses and attract immune cells to the tumor site. The versatility and multifaceted mechanisms of action of oncolytic viruses make them a promising therapeutic strategy for modulating the immune microenvironment in colon cancer, potentially overcoming resistance to conventional therapies and improving patient outcomes (Cook et al., 2018). 4.5 Modulating tumor-associated macrophages Tumor-associated macrophages (TAMs) can exhibit pro-tumor or anti-tumor phenotypes depending on the signals in the tumor microenvironment (Wang et al., 2021). Strategies to reprogram TAMs from a pro-tumor (M2) to an anti-tumor (M1) phenotype include the use of CSF-1R inhibitors, which have shown potential in enhancing the efficacy of other immunotherapies (Chamseddine et al., 2022). 4.6 Targeting myeloid-derived suppressor cells Myeloid-derived suppressor cells (MDSCs) are key immunosuppressive cells that inhibit T cell responses and promote tumor growth. Targeting MDSCs with agents that block their recruitment, differentiation, or function is a promising approach to enhance the efficacy of cancer immunotherapies(Yin et al., 2020). Strategies include the use of small molecule inhibitors and monoclonal antibodies that disrupt MDSC-mediated suppression (Guerrouahen et al., 2019; Wu et al., 2022).
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