Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 234-253 http://medscipublisher.com/index.php/cge 235 Furthermore, understanding the molecular and cellular mechanisms underlying immune responses within the TME is critical for identifying biomarkers that predict response to immunotherapy. For example, higher tumor mutational burden (TMB) has been associated with better responses to ICIs, as it likely reflects a greater neoantigen load that can be recognized by the immune system (Wang et al., 2020b). This study provides a comprehensive overview of the immune microenvironment of colorectal cancer and its impact on treatment, including the key components and dynamics of the colorectal cancer immune microenvironment. It discusses the roles of various immune cells, such as tumor-associated macrophages, dendritic cells, and T cells, in tumor progression and treatment response. The latest advances in therapeutic strategies aimed at modulating the immune microenvironment, including immune checkpoint inhibitors, vaccines, and combination therapies, are explored. This study highlights the critical importance of the immune microenvironment in colorectal cancer and its potential as a therapeutic target. Through systematic analysis, this paper offers scientific evidence and research directions for future colorectal cancer treatments. 2 Colon Cancer and the Immune Microenvironment 2.1 Overview of colon cancer pathogenesis Colon cancer is one of the most prevalent cancers worldwide, characterized by its complex pathogenesis involving genetic mutations, epigenetic alterations, and environmental factors. The disease often progresses from benign adenomas to malignant carcinomas through a series of well-defined stages known as the adenoma-carcinoma sequence. Key genetic mutations commonly associated with colon cancer include alterations in the APC, TP53, and KRAS genes, which contribute to unchecked cell proliferation and tumorigenesis (Schmitt and Greten, 2021). Additionally, microsatellite instability (MSI) and chromosomal instability (CIN) are significant pathways implicated in the pathogenesis of colon cancer, affecting the tumor's behavior and response to therapies (Bao et al., 2020). 2.2 The role of the immune system in cancer development The immune system plays a dual role in cancer development by both suppressing and promoting tumor growth. On one hand, immune surveillance mechanisms can detect and eliminate nascent tumor cells. On the other hand, chronic inflammation and immune evasion strategies employed by tumor cells can facilitate cancer progression (Frigerio et al., 2021). In colon cancer, the immune microenvironment is critically involved in shaping tumor development and response to treatment. The presence of immune cells such as cytotoxic T lymphocytes (CTLs), regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment influences the balance between anti-tumor immunity and immune suppression (Cao et al., 2022; Trimaglio et al., 2020). 2.3 Components of the tumor immune microenvironment The tumor immune microenvironment in colon cancer consists of various cellular and molecular components that interact to influence tumor growth and therapeutic response. 2.3.1 Immune cells Immune cells within the tumor microenvironment include both innate and adaptive immune cells. Tumor-associated macrophages (TAMs), dendritic cells (DCs), neutrophils, natural killer (NK) cells, and various subsets of T cells and B cells play distinct roles in modulating tumor progression. For instance, TAMs can exhibit either pro-tumor (M2) or anti-tumor (M1) phenotypes depending on their activation state and cytokine milieu. The infiltration and activation status of CTLs and Tregs are particularly crucial, as they can directly kill tumor cells or suppress immune responses, respectively (Cen et al., 2021; Wang et al., 2020b). 2.3.2 Cytokines and chemokines Cytokines and chemokines are critical signaling molecules in the tumor microenvironment that regulate immune cell recruitment, differentiation, and function. Pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β can promote tumorigenesis by enhancing tumor cell proliferation, survival, and angiogenesis. Conversely, anti-inflammatory cytokines such as IL-10 and TGF-β can suppress effective anti-tumor immune responses.
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