Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer

Abstract

Colorectal cancer remains one of the most important health challenges in our society. The development of cancer immunotherapies has fostered the need to better understand the anti-tumor immune mechanisms at play in the tumor microenvironment and the strategies by which the tumor escapes them. In this review, we provide an overview of the molecular interactions that regulate tumor inflammation. We particularly discuss immunomodulatory cell-cell interactions, cell-soluble factor interactions, cell-extracellular matrix interactions and cell-microbiome interactions. While doing so, we highlight relevant examples of tumor immunomodulation in colorectal cancer.

Development of an immune-related gene prognostic risk model and identification of an Immune infiltration signature in the tumor microenvironment of colon cancer

“…With the emergence of immunotherapy, the importance of TME has been emphasized [12]. Cancer cells disrupt the integrity of intestinal barrier through interactions with immune cells, stromal cells and extracellular matrix, which together form the TME [13,14]. The TME is not static but dynamic.…”

“…The differences in drug sensitivity and prognosis re ect that colon cancer is highly heterogeneous in the TME. Generally, speci c genetic and epigenetic alterations in colon cancer affect the composition of TME [13,15,16]. The development of colon cancer is inextricably linked to dysregulated TME.…”

The role of the tumor microenvironment in colorectal cancer and the potential therapeutic approaches

“… 8 , 31 , 32 Regulating immune cell infiltration into the pre‐metastatic niches or tumor is another way that direct tumor cells and TME interaction can affect inflammation. 33 Microenvironment cells stimulate the secretion of matrix remodeling enzymes, cytokines, chemokines, and growth factors. 34 Although cytokines are in charge of tumor suppression based on tumor microenvironment, they initiate cell transformation and progression in constant inflammation responses that result in a disrupted balance of pro‐ and anti‐inflammatory cytokines.…”

“…The weakness of the anti‐tumor response may result from the lack of proper reorganization of a primary signal to pathogens, down‐regulation of the immune system to avoid self‐harm or the involvement of the microenvironment to hinder any assessment of the immune system to the tumor cells 8,31,32 . Regulating immune cell infiltration into the pre‐metastatic niches or tumor is another way that direct tumor cells and TME interaction can affect inflammation 33 . Microenvironment cells stimulate the secretion of matrix remodeling enzymes, cytokines, chemokines, and growth factors 34 .…”

Exosome-Derived Non-Coding RNAs in the Tumor Microenvironment of Colorectal Cancer: Possible Functions, Mechanisms and Clinical Applications

“…TME is an important factor leading to the heterogeneity and targeted therapy of CRC ( 6 , 20 ). The composition of TME is influenced by both tumor features and patient state, which impacts disease progression, responsiveness to cancer therapy, and survival prognosis ( 21 ). A lot of research shows that TME plays a crucial role in tumor growth, metastasis, and drug resistance ( 22 ).…”