Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 234-253 http://medscipublisher.com/index.php/cge 234 Feature Review Open Access Modulating the Immune Microenvironment for Colon Cancer Therapy Jie Lian, Junhao Xu, Nanlin Huang, Haibo Lu Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, 150006, Heilongjiang, China Corresponding author: luhaibo@hrbmu.edu.cn Cancer Genetics and Epigenetics, 2024, Vol.12, No.5 doi: 10.5376/cge.2024.12.0024 Received: 21 Jul, 2024 Accepted: 31 Aug., 2024 Published: 10 Sep., 2024 Copyright © 2024 Lian et al., This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Lian J., Xu J.H., Huang N.L., and Lu H.B., 2024, Modulating the immune microenvironment for colon cancer therapy, Cancer Genetics and Epigenetics, 12(5): 234-253 (doi: 10.5376/cge.2024.12.0024) Abstract Colorectal cancer remains a significant challenge in cancer treatment due to its complex tumor microenvironment and immune evasion strategies. This study comprehensively examines the immune microenvironment of colorectal cancer and its impact on therapy, deeply exploring the critical roles of immune cells, cytokines, and the extracellular matrix in regulating tumor progression and treatment response. The study further investigates various therapeutic strategies to modulate the immune microenvironment, including immune checkpoint inhibitors, adoptive cell transfer therapy, cancer vaccines, and oncolytic viruses. Additionally, this study emphasizes the importance of personalized immunotherapy and the necessity of integrating multi-omics data to deeply understand and optimize therapeutic strategies. Future research should focus on overcoming immune resistance, enhancing immune memory, and utilizing biomarkers to predict treatment responses. The comprehensive analysis in this study highlights the potential of strategies targeting the immune microenvironment to improve clinical outcomes for colorectal cancer patients. Keywords Colon cancer; Immune microenvironment; Immunotherapy; Immune checkpoints; Cancer vaccines 1 Introduction Colon cancer, a leading cause of cancer-related mortality globally, poses significant challenges despite the advancements in medical interventions such as surgery, chemotherapy, and targeted therapies. The survival rate for patients diagnosed with advanced-stage colon cancer remains dismally low, emphasizing the urgent need for more effective treatment strategies (Cao et al., 2022). A growing body of evidence indicates that the tumor microenvironment (TME), particularly the immune microenvironment, plays a pivotal role in the progression and therapeutic response of colon cancer. The immune microenvironment comprises a complex network of immune cells, signaling molecules, and extracellular matrix components. These elements interact in ways that can either support or inhibit tumor growth. For instance, immune cells such as tumor-associated macrophages, dendritic cells, and T cells can influence the tumor’s behavior through various signaling pathways (Wang et al., 2020b). The intricate interplay within the immune microenvironment has profound implications for the development of therapeutic strategies. Tumors often exploit immune checkpoints—regulatory pathways that normally maintain self-tolerance and modulate the duration and amplitude of physiological immune responses—to evade immune detection. Immune checkpoint inhibitors (ICIs), which block these regulatory pathways, have shown promise in unleashing anti-tumor immune responses. However, the success of ICIs in colon cancer has been limited to a subset of patients, particularly those with microsatellite instability-high (MSI-H) tumors, highlighting the variability in immune microenvironment characteristics among patients (Bao et al., 2020; Lazarus et al., 2018). Recent research has underscored the potential of modulating the immune microenvironment to enhance the efficacy of existing therapies and develop new treatment modalities. Strategies such as combining ICIs with other forms of therapy, including oncolytic viruses and colony-stimulating factor 1 receptor (CSF-1R) inhibitors, have shown synergistic effects in preclinical models. These combination therapies work by reprogramming the immune microenvironment to favor anti-tumor immunity, increasing the infiltration and activity of cytotoxic T cells within the tumor (Shi et al., 2019).
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