The identification of TCF1+ progenitor exhausted T-cells in THRLBCL may predict a better response to PD-1/PD-L1 blockade

ABSTRACT: T-cell/histiocyte rich large B-cell lymphoma (THRLBCL) is a rare and aggressive variant of diffuse large B cell lymphoma (DLBCL) that usually affects young to middle-aged patients, with disseminated disease at presentation. The tumor microenvironment (TME) plays a key role in THRLBCL, due to its peculiar cellular composition (less than 10% neoplastic B-cells interspersed in a cytotoxic T-cell/histiocyte rich background). A significant percentage of THRLBCL is refractory to RCHOP-based regimens and to CAR-T therapy; thus, the development of a specific therapeutic approach for these patients still represents an unmet clinical need. To better understand the interaction of immune cells in THRLBCL TME and identify more promising therapeutic strategies, we compared the immune gene expression profiles of 12 THRLBCL and 10 DLBCL samples, using the Nanostring PanCancer Immune Profiling panel. Gene co-expression network analysis identified the predominant role of the PD-1/PD-L1 axis in the modulation of the immune response. Furthermore, the PD-1/PD-L1 activation was flanked by the overexpression of as many as 48 genes related to the functional exhaustion of T-cells. Globally, THRLBCL TME was highly interferon-inflamed and severely exhausted. The immune gene profiling findings strongly candidate THRLBCL for anti-PD-1 therapy, but also allowed us to take a step forward in understanding THRLBCL TME. Of therapeutic relevance, we identified a subset of TCF1+ progenitor exhausted T-cells enriched in THRLBCL patients. This subset of TCF1+ exhausted T-cells correlates with good clinical response to immune checkpoint therapy and may improve prediction of anti-PD-1 response in THRLBCL patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205919 | GEO | 2022/11/09

REPOSITORIES: GEO