The tumor microenvironment in hematologic malignancies: immune evasion, metabolic reprogramming, and therapeutic resistance

Hematological malignancies, including leukemia, lymphoma, and multiple myeloma, develop within and remain dependent on a complex and dynamic tumor microenvironment (TME). Malignant cells interact continuously with the cellular and molecular components of the TME, which play a critical role in shaping disease progression, therapeutic response, and immune evasion. The TME comprises mesenchymal stromal cells, immune cells, fibroblasts, endothelial cells, and a range of signaling molecules such as chemokines, cytokines, and extracellular vesicles, embedded within a heterogeneous extracellular matrix (ECM). This integrated network, along with recently established mechanisms, establishes a supportive niche that promotes malignant cell survival, clonal evolution, immune modulation, and therapy resistance. This review examines the cellular and molecular architecture of the hematologic TME and its influence on chemoresistance and immune suppression. It further discusses therapeutic interventions that aim to disrupt or reprogram the TME, thereby restoring therapeutic sensitivity and enhancing immune-mediated clearance.