CCR4 Blockade Diminishes Intratumoral Macrophage Recruitment and Augments Survival of Syngeneic Pancreatic Cancer-Bearing Mice

Khabipov, Aydar; Trung, Dung Nguyen; Linde, Julia van der; Miebach, Lea; LENZ, M; Erne, Felix; Bernstorff, Wolfram von; Schulze, Tobias; Kersting, Stephan; Bekeschus, Sander; Partecke, Lars Ivo

doi:10.3390/biomedicines11061517

Cited by 5 publications

(2 citation statements)

References 89 publications

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“…Besides CCR2, CCR4 is a receptor expressed on monocytes/macrophages that promotes their migration [ 45 , 46 ]. The CCL2/CCR4 axis plays a role as a chemoattractant of monocytes/macrophages in pancreatic ductal carcinoma (PDA) and in murine pancreatic cancer [ 47 , 48 , 49 ]. Therefore, it is a potential immunological target to suppress TAM formation; in fact, CCR4 blockade improves prognosis in pancreatic cancer [ 48 ].…”

Section: Recruitment Of Monocytes/macrophages Into Tumorsmentioning

confidence: 99%

New Strategies for Macrophage Re-Education in Cancer: An Update

Lampiasi

2024

IJMS

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The association between cancer and inflammation is well established. Chronic inflammation represents a fundamental step in the development and progression of some types of cancer. Tumors are composed of a heterogeneous population of infiltrating cells including macrophages, fibroblasts, lymphocytes, granulocytes, and mast cells, which respond to signals from the microenvironment and, in turn, produce cytokines, chemokines, transcription factors, receptors, and miRNAs. Recent data demonstrate that, in addition to classical (M1) and alternative (M2) macrophage subtypes, there are many intermediate subtypes that potentially play different roles in response to environmental stimuli. Tumors are infiltrated by macrophages called TAMs that mainly display an M2-like phenotype and tumor growth-permissive activities. There is a bidirectional interaction between tumor cells and tumor-infiltrating cells that determines macrophage polarization and ultimately tumor progression or regression. These complex interactions are still unclear but understanding them is fundamental for the development of new therapeutic strategies. Re-educating tumor-permissive macrophages into anti-tumor macrophages is a new focus of research. This review aims to analyze the most recent articles investigating the interplay between tumors, tumor-infiltrating cells, and TAMs, and the strategies for re-educating tumor-permissive macrophages.

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Section: Recruitment Of Monocytes/macrophages Into Tumorsmentioning

confidence: 99%

New Strategies for Macrophage Re-Education in Cancer: An Update

Lampiasi

2024

IJMS

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“…In vitro experiments showed that employing an anti-CCR4 antibody effectively decreased Treg cell counts, facilitating the activation of cancer/testis antigen-specific T cell responses [ 75 ]. Blocking CCR4 reduces the infiltration of TAMs and enhances survival in a syngeneic mouse model of pancreatic cancer [ 76 ]. CCL22 might serve as a promising biomarker of poor prognosis in cancer [ 77 ].…”

Section: Ccl22mentioning

confidence: 99%

Chemokines and Cytokines in Immunotherapy of Melanoma and Other Tumors: From Biomarkers to Therapeutic Targets

Reschke,

Enk,

Hassel

2024

IJMS

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Chemokines and cytokines represent an emerging field of immunotherapy research. They are responsible for the crosstalk and chemoattraction of immune cells and tumor cells. For instance, CXCL9/10/11 chemoattract effector CD8+ T cells to the tumor microenvironment, making an argument for their promising role as biomarkers for a favorable outcome. The cytokine Interleukin-15 (IL-15) can promote the chemokine expression of CXCR3 ligands but also XCL1, contributing to an important DC-T cell interaction. Recruited cytotoxic T cells can be clonally expanded by IL-2. Delivering or inducing these chemokines and cytokines can result in tumor shrinkage and might synergize with immune checkpoint inhibition. In addition, blocking specific chemokine and cytokine receptors such as CCR2, CCR4 or Il-6R can reduce the recruitment of tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs) or regulatory T cells (Tregs). Efforts to target these chemokines and cytokines have the potential to personalize cancer immunotherapy further and address patients that are not yet responsive because of immune cell exclusion. Targeting cytokines such as IL-6 and IL-15 is currently being evaluated in clinical trials in combination with immune checkpoint-blocking antibodies for the treatment of metastatic melanoma. The improved overall survival of melanoma patients might outweigh potential risks such as autoimmunity. However, off-target toxicity needs to be elucidated.

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