Genetic aberrations can shape the TME through several mechanisms. (1) Mutations that target molecules directly interacting with TME cells (eg, mutations in MHC-I components and NOTCH1); (2) Mutations that reprogram lymphoma cells (eg, MYC amplification) by changing the expression of membrane receptors for ECM and cells (eg, integrins), expression of suppressive molecules (eg, CD47), and pathway rewiring (eg, interleukin receptors) that makes lymphoma cells to thrive on certain TMEs; and (3) these mutations can also release into the extracellular space lymphoma products (eg, metabolites, cytokines) that induce short-range (ie, in an autocrine and/or paracrine manner) changes in cell subtypes and/or cell functionality favoring immunosuppression (eg, adenosine and inosine inhibiting CD8⁺ cytotoxic T cells) and TME polarization (eg, FGFR recruiting fibroblasts into CAFs) as well as long-range changes on distant organs that provide cells that infiltrate the TME (eg, inflammatory interleukins mobilizing monocytes from bone marrow).