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Curated Papers > In recent years, high-impact research on the "tumor microenvironment" (IF≥30, last 5 years)

Macrophages and Metabolism in the Tumor Microenvironment. ​

Literature Information ​

DOI10.1016/j.cmet.2019.06.001
PMID31269428
JournalCell metabolism
Impact Factor30.9
JCR QuartileQ1
Publication Year2019
Times Cited932
Keywordsfatty acid oxidation, glycolysis, hypoxia, immunosuppressive metabolites, immunotherapy
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN1550-4131
Pages36-50
Issue30(1)
AuthorsIlio Vitale, Gwenola Manic, Lisa M Coussens, Guido Kroemer, Lorenzo Galluzzi

TL;DR ​

This study explores the role of tumor-associated macrophages (TAMs) in the tumor microenvironment, highlighting their dual function in promoting tumor growth and therapy resistance while also exhibiting potential antitumor effects when activated. By elucidating the metabolic pathways that TAMs utilize to influence tumor progression, the research underscores their significance as promising targets for developing novel anticancer therapies.

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fatty acid oxidation · glycolysis · hypoxia · immunosuppressive metabolites · immunotherapy

Abstract ​

Tumor-associated macrophages (TAMs) constitute a plastic and heterogeneous cell population of the tumor microenvironment (TME) that can account for up to 50% of some solid neoplasms. Most often, TAMs support disease progression and resistance to therapy by providing malignant cells with trophic and nutritional support. However, TAMs can mediate antineoplastic effects, especially in response to pharmacological agents that boost their phagocytic and oxidative functions. Thus, TAMs and their impact on the overall metabolic profile of the TME have a major influence on tumor progression and resistance to therapy, de facto constituting promising targets for the development of novel anticancer agents. Here, we discuss the metabolic circuitries whereby TAMs condition the TME to support tumor growth and how such pathways can be therapeutically targeted.

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Primary Questions Addressed ​

  1. How do different subtypes of tumor-associated macrophages (TAMs) influence the metabolic pathways in the tumor microenvironment?
  2. What specific pharmacological agents have been shown to enhance the phagocytic and oxidative functions of TAMs, and what are their mechanisms of action?
  3. In what ways can the metabolic profiles of TAMs be manipulated to improve the efficacy of existing cancer therapies?
  4. What role does the interaction between TAMs and other immune cells in the tumor microenvironment play in shaping metabolic conditions that favor tumor progression?
  5. How can targeting the metabolic circuitries of TAMs lead to the development of novel anticancer agents that overcome therapy resistance?

Key Findings ​

Key Insights:

  1. Research Background and Purpose: Tumor-associated macrophages (TAMs) represent a significant component of the tumor microenvironment (TME), often making up to 50% of the cellular makeup in some solid tumors. Their dual role in tumor biology, acting both as facilitators of tumor progression and as potential mediators of antitumor immunity, presents a complex challenge in cancer treatment. The purpose of this research is to elucidate the metabolic pathways through which TAMs influence the TME, ultimately affecting tumor growth and resistance to therapeutic interventions. By understanding these mechanisms, the study aims to identify novel therapeutic targets for enhancing cancer treatment efficacy.

  2. Main Methods and Findings: The authors investigate the plasticity and heterogeneity of TAMs, highlighting their ability to adapt metabolically in response to the TME. They explore various metabolic circuitries that TAMs utilize to support tumor growth, such as nutrient supply and immunosuppressive factors that aid in tumor survival and proliferation. The study emphasizes the role of pharmacological agents that can enhance TAMs' phagocytic and oxidative functions, potentially shifting their role from tumor promoters to tumor fighters. Key findings indicate that targeting the metabolic pathways of TAMs could either inhibit tumor progression or enhance the efficacy of existing therapies.

  3. Core Conclusions: The research concludes that TAMs play a critical role in shaping the metabolic landscape of the TME, and their functions can be modulated through targeted therapeutic interventions. By understanding how TAMs metabolically condition the TME, researchers can develop strategies to exploit these pathways, offering new avenues for cancer treatment. The study reinforces the concept that TAMs are not merely passive components of the TME but are active participants in tumor biology, capable of influencing both tumor growth and response to therapies.

  4. Research Significance and Impact: This research is significant as it highlights the dualistic nature of TAMs, presenting them as both a challenge and an opportunity in cancer therapy. By focusing on the metabolic interactions within the TME, it paves the way for innovative therapeutic strategies that could enhance the effectiveness of current treatments. Understanding TAMs' metabolic roles may lead to the development of novel anticancer agents that can either inhibit their supportive functions or augment their antitumor capabilities. This work underscores the importance of targeting the TME, particularly TAMs, in the quest for more effective cancer therapies, potentially transforming the landscape of cancer treatment and improving patient outcomes.

Literatures Citing This Work ​

  1. Tumour Regression via Integrative Regulation of Neurological, Inflammatory, and Hypoxic Tumour Microenvironment. - Chang Hoon Lee;Jungsook Cho;Kyeong Lee - Biomolecules & therapeutics (2020)
  2. Harnessing tumor-associated macrophages as aids for cancer immunotherapy. - Xiaolei Li;Rui Liu;Xiao Su;Yongsha Pan;Xiaofeng Han;Changshun Shao;Yufang Shi - Molecular cancer (2019)
  3. 2-Hydroxyglutarate in Cancer Cells. - Petr Ježek - Antioxidants & redox signaling (2020)
  4. Immunological impact of cell death signaling driven by radiation on the tumor microenvironment. - Maria Esperanza Rodriguez-Ruiz;Ilio Vitale;Kevin J Harrington;Ignacio Melero;Lorenzo Galluzzi - Nature immunology (2020)
  5. Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses. - Clément Anfray;Aldo Ummarino;Fernando Torres Andón;Paola Allavena - Cells (2019)
  6. Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology. - Isaure Vanmeerbeek;Jenny Sprooten;Dirk De Ruysscher;Sabine Tejpar;Peter Vandenberghe;Jitka Fucikova;Radek Spisek;Laurence Zitvogel;Guido Kroemer;Lorenzo Galluzzi;Abhishek D Garg - Oncoimmunology (2020)
  7. Aberrant lipid metabolism in hepatocellular carcinoma cells as well as immune microenvironment: A review. - Bo Hu;Jian-Zhen Lin;Xiao-Bo Yang;Xin-Ting Sang - Cell proliferation (2020)
  8. Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function. - Haoxin Zhao;Lydia N Raines;Stanley Ching-Cheng Huang - Cells (2020)
  9. Wnt5a/CaMKII/ERK/CCL2 axis is required for tumor-associated macrophages to promote colorectal cancer progression. - Qing Liu;Jialin Song;Yue Pan;Dongdong Shi;Chaogang Yang;Shuyi Wang;Bin Xiong - International journal of biological sciences (2020)
  10. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. - Lorenzo Galluzzi;Ilio Vitale;Sarah Warren;Sandy Adjemian;Patrizia Agostinis;Aitziber Buqué Martinez;Timothy A Chan;George Coukos;Sandra Demaria;Eric Deutsch;Dobrin Draganov;Richard L Edelson;Silvia C Formenti;Jitka Fucikova;Lucia Gabriele;Udo S Gaipl;Sofia R Gameiro;Abhishek D Garg;Encouse Golden;Jian Han;Kevin J Harrington;Akseli Hemminki;James W Hodge;Dewan Md Sakib Hossain;Tim Illidge;Michael Karin;Howard L Kaufman;Oliver Kepp;Guido Kroemer;Juan Jose Lasarte;Sherene Loi;Michael T Lotze;Gwenola Manic;Taha Merghoub;Alan A Melcher;Karen L Mossman;Felipe Prosper;Øystein Rekdal;Maria Rescigno;Chiara Riganti;Antonella Sistigu;Mark J Smyth;Radek Spisek;John Stagg;Bryan E Strauss;Daolin Tang;Kazuki Tatsuno;Stefaan W van Gool;Peter Vandenabeele;Takahiro Yamazaki;Dmitriy Zamarin;Laurence Zitvogel;Alessandra Cesano;Francesco M Marincola - Journal for immunotherapy of cancer (2020)

... (922 more literatures)

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