Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy

Xu, Shumin; Wang, Congjian; Yang, Lingge; Wu, Jianhua; Li, Mengshu; Xiao, Peng; Xu, Zhiyong; Xu, Yongfeng; Wang, Kai

doi:10.3389/fimmu.2023.1199631

Cited by 17 publications

(7 citation statements)

References 200 publications

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“… 39 , 40 Tumor‐associated macrophages are immune cells that play a role in multiple stages of tumor development and can promote cancer growth and progression through inflammation associated with cancer. 41 Several types of macrophages have been identified, but current research has focused mainly on M1 and M2 macrophages. Mounting evidence indicates that a balanced proportion of M1/M2 macrophages can determine the outcome of an organ under conditions of inflammation or injury.…”

Section: Discussionmentioning

confidence: 99%

Regulator of G protein signaling 1 is a potential target in gastric cancer and impacts tumor‐associated macrophages

Wu,

Xu,

Yang

et al. 2024

Cancer Science

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Regulator of G protein signaling 1 (RGS1) is closely associated with the tumor immune microenvironment and is highly expressed in various tumors and immune cells. The specific effects of RGS1 in the dynamic progression from chronic gastritis to gastric cancer have not been reported, and the role of tumor‐associated macrophages (TAMs) is also unclear. In the present study, RGS1 was identified as an upregulated gene in different pathological stages ranging from chronic gastritis to gastric cancer by using Gene Expression Omnibus (GEO) screening together with pancancer analysis of The Cancer Genome Atlas and clinical prognostic analysis. The results indicated that RGS1 is highly expressed in gastric cancer and has potential prognostic value. We confirmed through in vivo experiments that RGS1 inhibited the proliferation of gastric cancer cells and promoted apoptosis, which was further corroborated by in vitro experiments. Additionally, RGS1 influenced cell migration and invasion. In our subsequent investigation of RGS1, we discovered its role in the immune response. Through analyses of single‐cell and GEO database data, we confirmed its involvement in immune cell regulation, specifically TAM activation. Subsequently, we conducted in vivo and in vitro experiments to confirm the involvement of RGS1 in polarizing M1 macrophages while indirectly regulating M2 macrophages through tumor cells. In conclusion, RGS1 could be a potential target for the transformation of chronic gastritis into gastric cancer and has a measurable impact on TAMs, which warrants further in‐depth research.

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Section: Discussionmentioning

confidence: 99%

Regulator of G protein signaling 1 is a potential target in gastric cancer and impacts tumor‐associated macrophages

Wu,

Xu,

Yang

et al. 2024

Cancer Science

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“…Moreover, the presence of immune-suppressive cells, including MDSCs [99], tumor-associated macrophages (TAMs) [100,101], tumor-associated dendritic cells (TADCs) [102], and tumor-associated neutrophils (TANs) [103] may upregulate other immune checkpoint molecules (i.e., PD-L1, CTLA-4, LAG-3, TIM-3, etc.) to evade immune surveillance and escape immune evasion dendritic cells (TADCs), tumorassociated neutrophils (TANs) and Treg, the immunesuppressive factors in the TME such as cytokines (e.g., IL-2, IL-10, TGF-b, VEGF, etc.)…”

Section: Cd47-targeted Therapies Including Antibody-based Therapies C...mentioning

confidence: 99%

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

CHEN,

GUO,

2024

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Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer, with the tumor microenvironment (TME) playing a pivotal role in modulating the immune response. CD47, a cell surface protein, has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy. However, the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood. This comprehensive review aims to provide an overview of CD47's multifaced role in TME regulation and immune evasion, elucidating its impact on various types of immunotherapy outcomes, including checkpoint inhibitors and CAR T-cell therapy. Notably, CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes, especially when combined with other immunotherapeutic approaches. The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47. Despite the demonstrated effectiveness of CD47-targeted therapies, there are potential problems, including unintended effects on healthy cells, hematological toxicities, and the development if resistance. Consequently, further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches, ultimately improving cancer treatment outcomes. Overall, this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

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“…These cytokines bind to the IL-4Ra receptor, which can activate JAK1 (or 3)/STAT6. This activation leads to the expression of a variety of proteins and cytokines, such as arginase 1 (Arg1), CD163, CD206, IL-10, and transforming growth factor B (TGF-β), which mediate the formation of an immunosuppressive and tumor-permissive microenvironment. , Understanding the interactions between the different components of the TME, including TAMs and tumor cells, is an essential step that may pave the way to identifying ways to improve response to different treatments, overcome treatment resistance and tumor progression, and reduce treatment-specific toxicity. However, at present, the cell–cell and cell–matrix interactions are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

“…They can be triggered by pathogen-associated molecular markers, such as lipopolysaccharide (LPS), or certain pro-inflammatory cytokines, such as interferon gamma (IFN-γ). This phenomenon is largely due to activation of the Janus kinase (JAK)/STAT1 axis and the downstream secretion of tumor necrosis factor-α (TNF-α), pro-inflammatory cytokines, such as interleukin 1 (IL-1), IL-6, IL-8 and IL-12, and reactive oxygen species, which promote the antitumor immune response. − M2 macrophages, on the other hand, are “alternatively activated” macrophages and participate in parasitic infection, tissue remodeling, wound restoration, and angiogenesis. ,, M2-like macrophages are considered to be the most common type of TAMs found in solid cancers. They can be activated by anti-inflammatory cytokines such as IL-4 and IL-13.…”

Section: Introductionmentioning

confidence: 99%

3D Coculture between Cancer Cells and Macrophages: From Conception to Experimentation

Quoniou,

Moreau,

Cachin

et al. 2023

ACS Biomater. Sci. Eng.

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A tumor is a complex cluster with many types of cells in the microenvironment that help it grow. Macrophages, immune cells whose main role is to maintain body homeostasis, represent in the majority of cancers the most important cell population. In this context, they are called tumor-associated macrophages (TAMs) because of their phenotype, which contributes to tumor growth. In order to limit the use of animals, there is a real demand for the creation of in vitro models able to represent more specifically the complexity of the tumor microenvironment (TME) in order to characterize it and evaluate new treatments. However, the two-dimensional (2D) culture, which has been used for a long time, has shown many limitations, especially in terms of tumor representation. The three-dimensional (3D) models, developed over the last 20 years, have made it possible to get closer to what happens in vivo in terms of phenotypic and functional characteristics. Due to their architectural similarity to in vivo tissues, they provide a more physiologically relevant in vitro system. Most recently, it is the development of 3D coculture models in which two or three cell lines are cultured together that has allowed a better representation of TME with cell−cell interactions. Unfortunately, there is no clear direction for the design of these models at this time. In this Review on the coculture between cancer cells and TAMs, an in-depth analysis is performed to answer multiple questions on the conception of these models: Which models to use, and with which material and cancer lineage? Which monocyte or macrophage lines should be added to the coculture? And how can these models be exploited?

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Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy

Cited by 17 publications

References 200 publications

Regulator of G protein signaling 1 is a potential target in gastric cancer and impacts tumor‐associated macrophages

Regulator of G protein signaling 1 is a potential target in gastric cancer and impacts tumor‐associated macrophages

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

3D Coculture between Cancer Cells and Macrophages: From Conception to Experimentation

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