Key Points
• Source: Clinical and Translational Medicine
• Conclusions: “Our findings suggest that CD70 can play a role in either tumour suppression or oncogenesis in DLBCL, likely via distinct immune evasion mechanisms, that is, impairing T cell priming or inducing T cell exhaustion. Characterisation of specific dysfunction of CD70 in DLBCL may thus provide opportunities for the development of novel targeted immuno-therapeutic strategies.”
• Chinese and Swedish researchers assessed the clinical relevance of CD70 genetic alterations and protein expression in 2 DLBCL cohorts of either Chinese or Swedish descent. They also conducted transcriptomic analysis to help determine the role of CD70 alterations in the tumor microenvironment, as well as testing CD70 blockade plus PD-L1 inhibitor in mouse models.
• The investigators demonstrated that CD70 genetic mutations were more common in the Chinese vs. Swedish cohort. CD70 changes led to a either 1) a decrease/loss of protein expression, 2) reduction/loss of CD27 binding, or 3) both. These changes could interfere with T-cell priming and independently predicted poor OS.
• The authors wrote, “Paradoxically, we observed that over-expression of CD70 protein was also associated with a poor treatment response, as well as an advanced disease stage and EBV infection. More exhausted CD8+ T cells were furthermore identified in CD70 high-expression DLBCLs. Finally, in a murine lymphoma model, we demonstrated that blocking the CD70/CD27 and/or PD1/PD-L1 interactions could reduce CD70+ lymphoma growth in vivo, by directly impairing the tumour cell proliferation and rescuing the exhausted T cells.”
• One limitation of the current study is its small sample size. Furthermore, the correlation of CD70 genetic mutations and protein overexpression with poor survival involved 2 separate cohorts (i.e., Chinese and Swedish).