{"doi":"10.3389/fimmu.2025.1612588","title":"Editorial: Exploring macrophage roles in cancer progression and therapeutic targeting","abstract":"The tumor microenvironment is a complex ecosystem where macrophages exhibit remarkable diversity and adaptability. Several contributions include a major focus on the critical role of macrophage heterogeneity and plasticity in cancer progression and immunotherapy, underscoring the need for a nuanced understanding of their function. The review by Stavrou et al. summarizes recent findings on distinct TAM subsets in the tumor microenvironment and their involvement in breast cancer progression, emphasizing the constant interplay between TAMs and breast cancer cells as a major contributor to disease progression. This interaction involves the polarization of macrophages toward a tumor-promoting phenotype, induction of epithelial-to-mesenchymal transition in cancer cells, and enhancement of cancer stem cell properties. The authors discuss the clinical relevance of these findings, focusing on how a better understanding of TAM involvement in breast cancer metastasis could lead to more effective treatment options. They suggest that a thorough characterization of individual patients' TAM signatures could facilitate the design of personalized treatment strategies and improve the prediction of treatment responses. The paper by Zhou et al. provides an overview of the role of macrophages in cancer immunotherapy, highlighting recent advances in understanding their complex functions within the tumor microenvironment. Macrophages are a major component of the immune infiltrate in many solid tumors and can exhibit both pro-and anti-tumor activities depending on their phenotype and the signals they receive. The review discusses how tumor-associated macrophages (TAMs) often adopt an immunosuppressive, pro-tumor phenotype that promotes cancer progression and metastasis. However, emerging research has revealed strategies to reprogram these TAMs or harness their anti-tumor potential for cancer therapy. The authors describe several approaches being explored to target macrophages in cancer immunotherapy. These include blocking macrophage recruitment to tumors, depleting TAMs, repolarizing TAMs from a pro-tumor M2-like phenotype to an anti-tumor M1-like phenotype, and enhancing macrophage phagocytosis of cancer cells. The paper also discusses combining macrophage-targeted therapies with other immunotherapies like immune checkpoint inhibitors. Additionally, it highlights new technologies like single-cell RNA sequencing that are providing deeper insights into macrophage heterogeneity and function in the tumor microenvironment. Overall, the review emphasizes that macrophages represent a promising but complex target for improving cancer immunotherapy, with ongoing research aimed at better understanding and manipulating their diverse roles in tumors.Beyond understanding the broad role of macrophage heterogeneity, many contributions have focused on elucidating the specific molecular mechanisms by which macrophages contribute to cancer progression. This includes investigating the intricate signaling pathways, interactions, and molecules that govern macrophage behavior within the tumor microenvironment. In the review article by Baig et al, the authors explore the role of adaptor proteins in regulating inflammation in macrophages. Adaptor proteins are non-catalytic proteins that act as molecular bridges between cell surface receptors and intracellular effector molecules, mediating proteinprotein interactions and modulating immune cell signaling. These proteins play critical roles in organizing signaling complexes, regulating protein localization, and modulating the intensity/duration of cellular responses. Some adaptor proteins can function to activate signaling pathways, while others inhibit them. This dichotomy offers an opportunity to affect and alter macrophage function. As such, this article comprehensively reviews 20 adaptor molecules that actively dampen inflammatory signaling pathways in macrophages. The authors discuss how these adaptor proteins regulate ","journal":"Frontiers in Immunology","year":2025,"id":565500,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1468868,"name":"Yu Kato","orcid":"0000-0003-1662-6983","position":1,"is_corresponding":false},{"id":447101,"name":"David Entenberg","orcid":"0000-0003-0422-7264","position":2,"is_corresponding":false},{"id":268415,"name":"George S. Karagiannis","orcid":"0000-0002-8808-707X","position":0,"is_corresponding":true}],"reference_count":3,"raw_metadata":null,"created_at":"2026-07-19T02:56:28.709936Z","pmid":"40406110","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}