Appearance
Monocytes in the Tumor Microenvironment.
Literature Information
| DOI | 10.1146/annurev-pathmechdis-012418-013058 |
|---|---|
| PMID | 33497262 |
| Journal | Annual review of pathology |
| Impact Factor | 34.5 |
| JCR Quartile | Q1 |
| Publication Year | 2021 |
| Times Cited | 164 |
| Keywords | cancer, immunotherapy, innate immunity, monocytes, tumor microenvironment |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 1553-4006 |
| Pages | 93-122 |
| Issue | 16() |
| Authors | Stefano Ugel, Stefania Canè, Francesco De Sanctis, Vincenzo Bronte |
TL;DR
This review discusses the dual roles of monocytes in cancer, highlighting their capacity to either support immune suppression or activate antitumor responses, influenced by the tumor microenvironment. Understanding the ontogeny, heterogeneity, and functions of monocytes is crucial for developing effective immunotherapies that can overcome the challenges posed by the immune-suppressive networks in tumors.
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cancer · immunotherapy · innate immunity · monocytes · tumor microenvironment
Abstract
Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various mechanisms that induce immune tolerance, angiogenesis, and increased dissemination of tumor cells. Yet monocytes can also give rise to antitumor effectors and activate antigen-presenting cells. This yin-yang activity relies on the plasticity of monocytes in response to environmental stimuli. In this review, we summarize current knowledge of the ontogeny, heterogeneity, and functions of monocytes and monocyte-derived cells in cancer, pinpointing the main pathways that are important for modeling the immunosuppressive tumor microenvironment.
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Primary Questions Addressed
- How do different subtypes of monocytes contribute to the immunosuppressive environment in various types of tumors?
- What specific environmental stimuli influence the plasticity of monocytes within the tumor microenvironment?
- In what ways can targeting monocyte-derived cells enhance the efficacy of current immunotherapies in cancer treatment?
- How do monocytes interact with other immune cells in the tumor microenvironment to either promote or inhibit tumor progression?
- What are the potential therapeutic strategies to modulate monocyte function in order to shift the balance towards antitumor immunity?
Key Findings
1. Research Background and Objectives: Immunotherapy has dramatically changed the landscape of cancer treatment, offering new hope for patients. However, its effectiveness is limited, as only a small subset of patients experience prolonged survival. A significant challenge is the presence of a complex immune-suppressive network established by tumors, which evolves through various systemic and local influences throughout tumor progression. Understanding the role of monocytes in this context is crucial, as they serve as a critical link between innate and adaptive immune responses. This review aims to elucidate the ontogeny, heterogeneity, and functional roles of monocytes and monocyte-derived cells within the tumor microenvironment, emphasizing their dual roles in promoting and inhibiting tumor progression.
2. Main Methods and Findings: The review synthesizes existing literature on monocytes, examining their development, diversity, and contributions to tumor biology. It identifies key mechanisms through which monocytes influence the tumor microenvironment, including the induction of immune tolerance, promotion of angiogenesis, and facilitation of tumor cell dissemination. The review highlights the plasticity of monocytes, which allows them to adapt their functions based on environmental cues, leading to both pro-tumor and anti-tumor effects. Additionally, it discusses the pathways involved in the modulation of the immunosuppressive environment, underscoring the complexity of monocyte interactions in cancer.
3. Core Conclusions: Monocytes exhibit a dual functionality within the tumor microenvironment, capable of fostering both tumor-promoting and tumor-inhibiting responses. Their ability to transition between these roles is heavily influenced by external stimuli, reflecting their plastic nature. The review concludes that understanding the specific pathways and mechanisms that govern monocyte behavior is essential for developing effective immunotherapeutic strategies. By targeting these pathways, it may be possible to shift the balance towards anti-tumor immunity, thereby enhancing the efficacy of cancer treatments.
4. Research Significance and Impact: This review sheds light on the complex role of monocytes in the tumor microenvironment, contributing to the broader understanding of cancer immunology. The insights gained may inform the development of novel therapeutic approaches aimed at reprogramming monocyte activity to counteract tumor-induced immune suppression. By addressing the dual nature of monocytes, researchers and clinicians can better strategize immunotherapy interventions, potentially improving outcomes for a larger population of cancer patients. This work not only enhances our comprehension of tumor biology but also paves the way for innovative treatments that leverage the immune system's potential against cancer.
Literatures Citing This Work
- Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities. - Yingyue Liu;Xiangxiang Zhou;Xin Wang - Journal of hematology & oncology (2021)
- Fatal cytokine release syndrome by an aberrant FLIP/STAT3 axis. - Chiara Musiu;Simone Caligola;Alessandra Fiore;Alessia Lamolinara;Cristina Frusteri;Francesco Domenico Del Pizzo;Francesco De Sanctis;Stefania Canè;Annalisa Adamo;Francesca Hofer;Roza Maria Barouni;Andrea Grilli;Serena Zilio;Paolo Serafini;Evelina Tacconelli;Katia Donadello;Leonardo Gottin;Enrico Polati;Domenico Girelli;Ildo Polidoro;Piera Amelia Iezzi;Domenico Angelucci;Andrea Capece;Ying Chen;Zheng-Li Shi;Peter J Murray;Marco Chilosi;Ido Amit;Silvio Bicciato;Manuela Iezzi;Vincenzo Bronte;Stefano Ugel - Cell death and differentiation (2022)
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- The Versatile Roles of Cancer-Associated Fibroblasts in Colorectal Cancer and Therapeutic Implications. - Longfei Deng;Nianfen Jiang;Jun Zeng;Yi Wang;Hongjuan Cui - Frontiers in cell and developmental biology (2021)
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- Identification and Comprehensive Prognostic Analysis of a Novel Chemokine-Related lncRNA Signature and Immune Landscape in Gastric Cancer. - Xiaolong Liang;Gangfeng Yu;Lang Zha;Xiong Guo;Anqi Cheng;Chuan Qin;Han Zhang;Ziwei Wang - Frontiers in cell and developmental biology (2021)
- A Novel Risk Model Identified Based on Pyroptosis-Related lncRNA Predicts Overall Survival and Associates With the Immune Landscape of GC Patients. - Tingting Xu;Hanxin Gu;Changsong Zhang;Wushuang Zhang;Xiaolong Liang;Xiaoxia Cheng - Frontiers in genetics (2022)
- Defective Patient NK Function Is Reversed by AJ2 Probiotic Bacteria or Addition of Allogeneic Healthy Monocytes. - Meng-Wei Ko;Kawaljit Kaur;Tahmineh Safaei;Wuyang Chen;Christine Sutanto;Paul Wong;Anahid Jewett - Cells (2022)
... (154 more literatures)
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