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Review
. 2024 Oct 15;16(10):4064-4079.
doi: 10.4251/wjgo.v16.i10.4064.

Research progress of tumor-associated macrophages in immune checkpoint inhibitor tolerance in colorectal cancer

Qi Fan  1 , Zheng-Wei Fu  1 , Ming Xu  1 , Feng Lv  1 , Jia-Song Shi  1 , Qi-Qi Zeng  2 , De-Hai Xiong  3
Affiliations
Review

Research progress of tumor-associated macrophages in immune checkpoint inhibitor tolerance in colorectal cancer

Qi Fan et al. World J Gastrointest Oncol. .

Abstract

The relevant mechanism of tumor-associated macrophages (TAMs) in the treatment of colorectal cancer patients with immune checkpoint inhibitors (ICIs) is discussed, and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies. As a class of drugs widely used in clinical tumor immunotherapy, ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system. The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly. The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs. ICIs can regulate the phenotypic function of TAMs, and TAMs can also affect the tolerance of colorectal cancer to ICI therapy. TAMs play an important role in ICI resistance, and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.

Keywords: Colorectal cancer; Immune checkpoint inhibitor resistance; Review; Tumor microenvironment; Tumor-associated macrophages.

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Conflict of interest statement

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Figures

Figure 1
Figure 1
Immunogenicity and effects of immune microenvironment on cold and hot. NK: Natural killer; Treg: Regulatory T cell.
Figure 2
Figure 2
M2 macrophage subtypes. IL: Interleukin; TLR: Toll-like receptor; TGF: Transforming growth factor; CXCL: C-X-C motif chemokine ligand; CCL: C-C motif chemokine ligand; TNF: Tumor necrosis factor; VEGF: Vascular endothelial growth factor; Arg-1: Arginase-1.
Figure 3
Figure 3
Targeting effector cells with bispecific antibodies for cancer therapy. NK: Natural killer; EPCAM: Epithelial cell adhesion molecule; PSMA: Prostate-specific membrane antigen; BCMA: Bulbospinal muscular atrophy.
Figure 4
Figure 4
T cell co-stimulation and co-inhibition. TCR: T cell receptor; MHC: Major histocompatibility complex; CTLA: Cytotoxic T-lymphocyte-associated protein.
Figure 5
Figure 5
Mechanisms of immune evasion in colorectal cancer by cancer stem cells. CSC: Cancer stem cell; TME: Tumor microenvironment; TCR: T cell receptor; MHC: Major histocompatibility complex; MDSC: Myeloid-derived suppressor cell; PD-L1: Programmed cell death ligand 1; PD-1: Programmed cell death protein 1; STAT 3: Signal transducer and activator of transcription 3; AP-1: Activating protein-1; HLA: Human leukocyte antigen; IFNAR1: Interferon alpha/beta receptor 1; Treg: Regulatory T cell; IL: Interleukin; TGF: Transforming growth factor.
Figure 6
Figure 6
Effects of M2-type polarization from the tumor microenvironment. VEGF: Vascular endothelial growth factor; Th1: T helper 1; Treg: Regulatory T cell.
See this image and copyright information in PMC

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