Diffuse large B-cell lymphoma (DLBCL) is infiltrated with activated CD8 + T-cells despite immune checkpoint signaling

• Published in: Blood research Vol. 57; no. 2; pp. 117 - 128
• Main Authors: Greenbaum, Adam M, Fromm, Jonathan R, Gopal, Ajay K, Houghton, A McGarry
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis 30-06-2022; 대한혈액학회
• Subjects: Original; 병리학; Lymphoma; Immune checkpoint inhibition; immune microenvironment
• ISSN: 2287-979X; 2288-0011
• DOI: 10.5045/br.2022.2021145

B-cell non-Hodgkin lymphomas (NHL) are hematologic malignancies that arise in the lymph node. Despite this, the malignant cells are not cleared by the immune cells present. The failure of anti-tumor immunity may be due to immune checkpoints such as the PD-1/PDL-1 axis, which can cause T-cell exhaustion. Unfortunately, unlike Hodgkin lymphoma, checkpoint blockade in NHL has shown limited efficacy.
We performed an extensive functional analysis of malignant and non-malignant lymph nodes using high dimensional flow cytometry. We compared follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and lymph nodes harboring reactive hyperplasia (RH).
We identified an expansion of CD8+PD1+ T-cells in the lymphomas relative to RH. Moreover, we demonstrate that these cells represent a mixture of activated and exhausted T-cells in FL. In contrast, these cells are nearly universally activated and functional in DLBCL. This is despite expression of counter-regulatory molecules such as PD-1, TIM-3, and CTLA-4, and the presence of regulatory T-cells.
These data may explain the failure of single-agent immune checkpoint inhibitors in the treatment of DLBCL. Accordingly, functional differences of CD8+ T-cells between FL and DLBCL may inform future therapeutic targeting strategies.