Peripheral T cell lymphomas (PTCLs) are highly heterogeneous tumors, displaying distinct clinical and biological features. The pathogenesis and normal counterpart of such entities have been elusive for decades. Recent studies have, however, disclosed key mechanisms of peripheral T cell transformation, including (a) the deregulation of signaling pathways controlling T cell development, differentiation, and maturation; (b) the remodeling of the peritumor microenvironment; and (c) the virus-mediated rewiring of T cell biology. Uncovering the molecular mechanisms of T cell transformation will help elucidate the peculiar clinical and pathological features of each PTCL entity and will lead to the characterization of novel antitumor therapies. These therapies will combine conventional and new-generation compounds with immune-modulating agents to ablate both the neoplastic cells and the tumor-supporting microenvironment. This review addresses the pathogenic mechanisms of PTCLs, with special attention paid to novel therapeutic strategies for the clinical management of such aggressive tumors.
Keywords: PTCL; cell progression; cell transformation; genetic defects; microenvironment; peripheral T cell lymphoma; signaling pathways; target therapies.