The prognosis is bad for one of the aggressive peripheral T-cell neoplasms, adult T-cell leukemia/lymphoma (ATLL). The development of ATLL pathogenesis was consistently shown to be characterized by escape from adaptive immunity. Natural killer (NK) cell-mediated immunity is a form of immunity, although the processes by which ATLL cells avoid it were not well known. For a study, researchers sought to demonstrate how ATLL cell susceptibility to NK-cell mediated cytotoxicity against ATLL cells was influenced by CD48 expression in ATLL cells. 

Through unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening with 2 ATLL-derived cell lines, they identified CD48 as one of the best-enriched genes whose deletion conferred resistance to YT1-NK cell line-mediated cytotoxicity. Human primary NK cells with diminished interferon-γ (IFN-γ) induction and degranulation were used to establish that CD48-knockout ATLL cells can avoid NK-cell effector activity. 

They discovered that CD48 expression in primary ATLL cells decreased as the illness advanced. Further evidence that CD48 is a crucial component in malignant T-cell evasion of NK-cell surveillance may be found in different subgroups of aggressive peripheral T-cell lymphomas (PTCLs), which similarly exhibited lower quantities of CD48 than normal T cells. 

The study, therefore, showed that CD48 expression is probably essential for malignant T-cell lymphoma cells to control NK-cell-mediated immunity and justifies further research into CD48 as a molecular biomarker in NK-cell-associated immunotherapies.

Reference: ashpublications.org/blood/article/140/18/1951/486093/Genome-wide-CRISPR-screens-identify-CD48-defining