Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, as prognosticators in diffuse large B cell lymphoma: A population-based study

Keane, Colm, Vari, Frank, Hertzberg, Mark, Lê Cao, Kim-Anh, Green, Michael R., Han, Erica, Seymour, John F., Hicks, Rodney J., Gill, Devinder, Crooks, Pauline, Gould, Clare, Jones, Kimberley, Griffiths, Lyn R., Talaulikar, Dipti, Jain, Sanjiv, Tobin, Josh, & Gandhi, Maher K. (2015) Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, as prognosticators in diffuse large B cell lymphoma: A population-based study. Lancet Haemotology, 2(10), e445-e455.

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Abstract

Background

Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured despite initial R-CHOP. Although the prognostic importance of the tumour microenvironment (TME) is established, the optimal strategy to quantify it is unknown.

Methods

The relationship between immune-effector and inhibitory (checkpoint) genes was assessed by NanoString™ in 252 paraffin-embedded DLBCL tissues. A model to quantify net anti-tumoural immunity as an outcome predictor was tested in 158 R-CHOP treated patients, and validated in tissue/blood from two independent R-CHOP treated cohorts of 233 and 140 patients respectively.

Findings

T and NK-cell immune-effector molecule expression correlated with tumour associated macrophage and PD-1/PD-L1 axis markers consistent with malignant B-cells triggering a dynamic checkpoint response to adapt to and evade immune-surveillance. A tree-based survival model was performed to test if immune-effector to checkpoint ratios were prognostic. The CD4CD8:(CD163/CD68)PD-L1 ratio was better able to stratify overall survival than any single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO). Tissue findings were validated in 233 DLBCL R-CHOP treated patients. Furthermore, within the blood of 140 R-CHOP treated patients immune-effector:checkpoint ratios were associated with differential interim-PET/CT+ve/-ve expression.

Impact and interest:

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ID Code: 94392
Item Type: Journal Article
Refereed: Yes
Keywords: PD.1, PD-L1
DOI: 10.1016/S2352-3026(15)00150-7
ISSN: 2352-3026
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2015 Elsevier
Copyright Statement: Licensed under the Creative Commons Attribution; Non-Commercial; No-Derivatives 4.0 International. DOI: 10.1016/S2352-3026(15)00150-7
Deposited On: 05 Apr 2016 04:35
Last Modified: 05 Dec 2016 15:13

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