Prognostic effects and immune biomarkers associated with gasdermin protein expression in diffuse large B-cell lymphoma 4783

Abstract Description Pyroptosis has emerged as a novel form of programmed cell death implicated in tumorigenesis and antitumor immunity. To gain knowledge on the role of pyroptosis in diffuse large B-cell lymphoma (DLBCL), we assessed expression of cleaved gasdermin D (GSDMD), GSDME, and GSDMC by immunohistochemistry (IHC) in a large number of DLBCL specimens, and correlated the expression to patient survival and immune biomarkers quantified by multiplex fluorescent IHC, separately in two subcohorts treated by R-CHOP or CHOP chemotherapy. We found that cleaved GSDMD cytoplasmic expression was significantly associated with better survival of patients with DLBCL, increased CD38+ M1-like macrophages (CD68+CD163- or CD11c+), and higher CD38+ percentages in both two subcohorts, as well as lower PD-L1 expression in macrophages and PD-1 expression in T cells in the R-CHOP cohort (PD-1 and PD-L1 were not evaluated in the CHOP cohort). In contrast, GSDME was mainly expressed in endothelial cells, and showed significantly unfavorable prognostic effects and associations with higher CD31+ and CD3+ cell densities in both two subcohorts. In addition, GSDME+ and high GSDMC expression were associated with higher CD38+ cell densities (including CD38+ M1-like macrophages) and percentages in the R-CHOP cohort, whereas GSDME+ was associated with increased M2-like macrophages in the CHOP cohort. Together, these prognostic and correlative results indicate that gasdermins and pyroptosis have important roles in DLBCL. Funding Sources R01CA233490, Duke University startup fund Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)