Prognostic Impact of Tumor-Associated Macrophages on Survival Is Checkpoint Dependent in Classical Hodgkin Lymphoma
Open Access
- 4 April 2020
- Vol. 12 (4), 877
- https://doi.org/10.3390/cancers12040877
Abstract
Tumor microenvironment and immune escape affect pathogenesis and survival in classical Hodgkin lymphoma (cHL). While tumor-associated macrophage (TAM) content has been associated with poor outcomes, macrophage-derived determinants with clinical impact have remained undefined. Here, we have used multiplex immunohistochemistry and digital image analysis to characterize TAM immunophenotypes with regard to expression of checkpoint molecules programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO-1) from the diagnostic tumor tissue samples of 130 cHL patients, and correlated the findings with clinical characteristics and survival. We show that a large proportion of TAMs express PD-L1 (CD68+, median 32%; M2 type CD163+, median 22%), whereas the proportion of TAMs expressing IDO-1 is lower (CD68+, median 5.5%; CD163+, median 1.4%). A high proportion of PD-L1 and IDO-1 expressing TAMs from all TAMs (CD68+), or from CD163+ TAMs, is associated with inferior outcome. In multivariate analysis with age and stage, high proportions of PD-L1+ and IDO-1+ TAMs remain independent prognostic factors for freedom from treatment failure (PD-L1+CD68+/CD68+, HR = 2.63, 95% CI 1.17–5.88, p = 0.019; IDO-1+CD68+/CD68+, HR = 2.48, 95% CI 1.03–5.95, p = 0.042). In contrast, proportions of PD-L1+ tumor cells, all TAMs or PD-L1− and IDO-1− TAMs are not associated with outcome. The findings implicate that adverse prognostic impact of TAMs is checkpoint-dependent in cHL.Funding Information
- Academy of Finland (311171)
- Helsingin Yliopisto (NA)
- Helsingin ja Uudenmaan Sairaanhoitopiiri (TYH2015401)
This publication has 38 references indexed in Scilit:
- Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphomaHematology, 2017
- Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-Sternberg cells in Hodgkin lymphomaBlood, 2017
- High proportions of PD-1+ and PD-L1+ leukocytes in classical Hodgkin lymphoma microenvironment are associated with inferior outcomeBlood Advances, 2017
- IDO1: An important immunotherapy target in cancer treatmentInternational Immunopharmacology, 2017
- Microenvironmental interactions in classical Hodgkin lymphoma and their role in promoting tumor growth, immune escape and drug resistanceCancer Letters, 2016
- PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict OutcomeJournal of Clinical Oncology, 2016
- The immune microenvironment in Hodgkin lymphoma: T cells, B cells, and immune checkpointsHaematologica, 2016
- Programmed death-1 pathway in cancer and autoimmunityClinical Immunology, 2014
- Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancerCancer Immunology, Immunotherapy, 2014
- Molecular Pathogenesis of Hodgkin's Lymphoma: Increasing Evidence of the Importance of the MicroenvironmentJournal of Clinical Oncology, 2011