Looking ahead to targeting macrophages by CAR T- or NK-cells in blood cancers.

Ciprian Tomuleasa, Hermann Einsele, Diana Cenariu, David Kegyes, Paul Alexandru Milea, Andreea-Isabella Mazga, Adrian-Bogdan Tigu, Madalina Nistor, Radu Tomai, Sanda Buruiana, Alina Daniela Tănase

Journal: Expert opinion on therapeutic targets 2025;28(9):779-787

PMID: 39235181

Abstract

INTRODUCTION

The bone marrow microenvironment (BME) is critical for healthy hematopoiesis and is often disrupted in hematologic malignancies. Tumor-associated macrophages (TAMs) are a major cell type in the tumor microenvironment (TME) and play a significant role in tumor growth and progression. Targeting TAMs and modulating their polarization is a promising strategy for cancer therapy.

AREAS COVERED

In this review, we discuss the importance of TME and different multiple possible targets to modulate immunosuppressive TAMs such as: CD123, Sphingosine 1-Phosphate Receptors, CD19/CD1d, CCR4/CCL22, CSF1R (CD115), CD24, CD40, B7 family proteins, MARCO, CD47, CD163, CD204, CD206 and folate receptors.

EXPERT OPINION

Innovative approaches to combat the immunosuppressive milieu of the tumor microenvironment in hematologic malignancies are of high clinical significance and may lead to increased survival, improved quality of life, and decreased toxicity of cancer therapies. Standard procedures will likely involve a combination of CAR T/NK-cell therapies with other treatments, leading to more comprehensive cancer care.

Address: Department of Hematology/Medfuture Research Center for Advanced Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.; Department of Hematology, Ion Chiricuta Cancer Center, Cluj-Napoca, Romania.; Department of Hematology, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova.; Department of Hematology/Medfuture Research Center for Advanced Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.; Department of Internal Medicine II, Hematology, University Hospital Würzburg, Würzburg, Germany.; Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.; Department of Hematology/Medfuture Research Center for Advanced Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.; Department of Hematology, Ion Chiricuta Cancer Center, Cluj-Napoca, Romania.; Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.

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