When killers become thieves: trogocytosed PD-1 inhibits NK cells in cancer

Hasim et al (BioRxiv). DOI: 10.1101/2020.06.26.174342

 

Keywords

  • NK cells

  • PD-1 blockade

  • trogocytosis

Main Findings

  • PD-1 is acquired by NK cells from tumor cells (here, PD-1-expressing T cell lymphomas) via trogocytosis

  • Trogocytosis of PD-1 is dependent upon SLAM receptors

  • PD-1 blockade controls tumor growth in part due to reversal of inhibitory programming of NK cells

  • Above findings (in mouse models) were corroborated in human multiple myeloma (NK cells were found to acquire PD-1 through trogocytosis)

Limitations

  • Inhibitory function of PD-1 on human multiple myeloma cells was not established; unclear if the findings from mice in this respect are replicable in humans 

  • Interesting findings with clinical implications, but very few cancers have PD-1 expression. Clinically, these findings will likely only be relevant in select hematologic malignancies. However, the general finding that trogocytosis of markers from tumor cells by immune cell populations is important and should be studied in more depth

Significance/Novelty

This preprint is a major contribution to resolving the controversy of PD-1 expression on NK cells and the clinical ramifications of this expression. The paper represents a major advance regarding mechanistic insights into how PD-1 can be acquired exogenously and the involvement of SLAM receptors in this process. Further, it was previously appreciated that NK cells exert anti-tumor activity in the context of PD-1 blockade; this preprint explains why this is, as the PD-1 acquired via trogocytosis is functional and confers suppressive function to NK cells in the tumor microenvironment. Overall, this preprint highlights the importance of trogocytosis as a mechanism for acquisition of immunomodulatory receptors and resolves a previously unanswered question regarding the expression of and role of PD-1 expression on NK cells. Taken together, these data widen our understanding of pathways of immune resistance by tumor cells, and provide insights into how to develop better immunotherapies for cancer. 

Credit 

Reviewed by Jenna Newman as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai and the Kennedy Institute of Rheumatology, University of Oxford. Follow her on Twitter