As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T‐cell function, a key mechanism for antitumor immunity, of exosomes derived from three melanoma‐related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose‐dependently suppressed T‐cell proliferation. In contrast, Cloudman S91 exosomes promoted T‐cell proliferation and Melan‐A exosomes had a negligible effect on primary CD8+ T cells. Mechanistically, transcript profiling suggested that exosomal mRNA is enriched for full‐length mRNAs that target immune‐related pathways. Interestingly, B16F0 exosomes were unique in that they contained both protein and mRNA for PTPN11, which inhibited T‐cell proliferation. Collectively, the results suggest that upregulation of PTPN11 by B16F0 exosomes to tumor infiltrating lymphocytes would bypass the extracellular control of the immune checkpoints.