Innate Immune Cell Infiltration Induced by Polatuzumab Vedotin Contributes to the Antitumor Effect in Mouse Models

Introduction: Polatuzumab vedotin (Pola) is an antibody-drug conjugate approved for the treatment of diffuse large B-cell lymphoma (DLBCL). Several reports suggest that the tumor microenvironment influences the outcome of DLBCL treatments; with Pola, however, the link between tumor microenvironment and treatment outcome remains unclear. Objectives and Methods: We analyzed the relationship between the antitumor effect of Pola and immune status, focusing on innate immune cells in the tumor microenvironment by utilizing a xenograft mouse model and a syngeneic mouse model. Results: In the DB (DLBCL cell line) xenograft model, Pola induced infiltration of macrophages and natural killer cells, which contributed to the antitumor effect of Pola. Moreover, Pola induced the release of several damage-associated molecular patterns from DB cells and enhanced the migration of immune cells under ex vivo co-culture conditions. A syngeneic mouse model also confirmed the involvement of innate immune cells in the Pola effect. Conclusion: This study demonstrates that Pola treatment alters MΦ and NK cell infiltration in tumors, highlighting these innate immune cells' essential contribution to Pola's antitumor activity. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.