Tee-ing up a New Follicular Lymphoma Classification System

Abstract

In this issue of Blood Cancer Discovery, Han and colleagues find that follicular lymphomas (FL) can be stratified into distinct classes with clinical and functional relevance based on their T-cell subset composition. Their findings further indicate that pairing of FL cell MHCII expression with specific T-cell markers may represent a useful diagnostic approach to select patients for particular immunotherapies or immune augmentation therapies independent of genetic profiling. See related article by Han et al., p. 428 (4).

Figure 1.

Integration of mutation profiles, scRNA-seq, RNA deconvolution, and histologic analyses identifies biologically, clinically, and perhaps therapeutically distinct types of FL. Top: T cell–based mRNA deconvolution analysis yielded four classes of FLs as indicated, based on their composition of T-cell subsets, highlighting some of the main T-cell subset variations associated with each type. Middle: FLs are composed of a heterogeneous mix of cells resulting in complex and often rich LMEs. This includes CD4_CTLs, a cell type not previously associated with the FL LME. Bottom: FLs can be segregated into MHCII low (similar to the depleted) or MHCII high classes that feature enrichment for distinct T-cell subpopulations, immune, and checkpoint profiles, potentially suggesting distinct immune therapy approaches for each class. Hence, MHCII staining constitutes a powerful, putative biomarker for precision immune diagnostics and therapy in FL.