Immune checkpoint blockade and CAR T-cell therapy in T-cell/histiocyte-rich large B-cell lymphoma: Challenges and opportunities

Abstract

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a highly aggressive large B-cell lymphoma defined by a paucity of malignant B cells amidst a dense infiltrate of reactive T cells and histiocytes. The unique tumor microenvironment (TME) of THRLBCL, marked by extensive immune infiltration and high PD-L1 expression, poses significant challenges for immunotherapies. This review explores the therapeutic potential and resistance mechanisms of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell therapy in THRLBCL. While ICIs show promise due to the immune-suppressive nature of the TME, CAR T-cell therapy has demonstrated limited efficacy, often hindered by primary resistance and early relapse. Combining CAR T-cell therapy with ICIs and Bruton tyrosine kinase (BTK) inhibitors and developing novel CAR constructs targeting multiple antigens are potential strategies to enhance treatment outcomes. Further prospective studies are essential to corroborate these strategies and improve the prognosis for this challenging lymphoma subtype.

Keywords: CAR T-cell; Immune checkpoint inhibitors; T-cell/histiocyte-rich large B-Cell lymphoma; Tumor microenvironment.

Graphical abstract

Fig. 1

Challenges for CAR-T cell therapy in T-cell/histiocyte-rich Large B-cell Lymphoma (Created with BioRender.com.).