PD-L1+ macrophages are associated with favorable features in primary mediastinal (thymic) large B-cell lymphoma

Raphael E. Steiner, Edwin R. Parra, Francisco Vega, Lei Feng, Jason R. Westin, Sattva S. Neelapu, Paolo Strati, Michael R. Green, Christopher R. Flowers, Luisa M. Solis, Ignacio I. Wistuba, Sairah Ahmed, Ranjit Nair, Fredrick B. Hagemeister, Mansoor Noorani, Mario L. Marques-Piubelli

Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a rare, aggressive subtype of non-Hodgkin lymphoma and has a complex inflammatory microenvironment. Although most patients can be cured with standard-of-care immunochemotherapy, patients who have disease relapse have an unfavorable prognosis. Pre-treatment prognostic biomarkers in PMBCL are needed. In this retrospective study, we analyzed the clinical features and outcomes of PMBCL patients and their association with immune cell subpopulations identified by multiplex immunofluorescence at initial diagnosis. Two different antibody panels were used to assess macrophages in tissue biopsy specimens collected before the initiation of induction therapy. Twelve PMBCL patients, including five patients who had disease relapse, were included in the analysis. At a median follow-up time of 32.2 months, the median progression-free and overall survival durations were not reached. Our findings suggest that a high density of PD-L1+ macrophages is associated with favorable features, such as early disease stage and the absence of B-symptoms, and indicate that a high percentage of PD-L1+ macrophages and high densities of CD30+PD-L1+ cells and CD30+ cells might be associated with a lower risk of relapse within 12 months of therapy initiation. Further studies are needed to develop a biomarker signature predictive of treatment response with therapeutic consequences for patients with newly diagnosed PMBCL.