Tumour-associated macrophages (TAMs) are key orchestrators of the immune and stromal microenvironment, affecting cancer progression, metastatic ability, and the tissue’s inflammatory balance. In this issue of the Central European Journal of Immunology (CEJI), Lu et al. report that colorectal cancer (CRC)-derived LAMA1 promotes macrophage M2 polarisation by activating the EGFR–AKT–CREB pathway. Their study offers a new mechanistic understanding of how tumour-derived extracellular matrix (ECM) components can influence macrophage function and, in turn, the tumour microenvironment (TME) [1].

While cytokines and soluble mediators have long been recognised as orchestrators of macrophage phenotype, Lu et al. expand this understanding by demonstrating that a basement membrane component, namely LAMA1, can serve as a signalling mediator rather than solely as a structural component. Identifying the EGFR–AKT–CREB pathway as an intracellular signalling pathway regulating macrophages enhances our understanding of how tumour cells may indirectly influence immune responses [1].

This research aligns with a broader trend observed in CEJI publications over the past 2 years, where several studies have explored macrophage plasticity and the complex dialogue between the tumour and immune compartments.

For instance, Huang et al. demonstrated that exposure to the anaesthetic sevoflurane alters macrophage-like cell polarisation in a cervical-cancer model [2]. Similar findings have been reported for lung adenocarcinoma, where ANKRD22 expression facilitated angiogenesis by skewing macrophage-like cells’ activation states [3]. Collectively, these studies, and now the contribution by Lu et al., as well as recently published reports in other journals, emphasise that a single pathway does not govern TAM polarisation but results from the integration of multiple environmental and molecular signals [4, 5]. From a scientific standpoint, the study reinforces a crucial message: macrophages interpret not only cytokine gradients, but also structural and biochemical cues derived from the ECM [6, 7]. This recognition broadens our understanding of immune regulation within tumours, positioning the ECM as an active participant in shaping immune cell function [8].

Taken together, the work by Lu et al. adds a valuable layer to the evolving narrative of macrophage biology in cancers [1]. By uncovering a previously unappreciated ECM-to-macrophage signalling route, this study enriches our mechanistic understanding of tumour–immune crosstalk. It highlights the ongoing need for experimental systems that bridge models with physiological complexity.