Programmed cell death ligand 1 (PD-L1) expressing myeloid cells and their relevance to cancer immunotherapy
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Embargo End Date
2026-07-15
ICR Authors
Authors
Julve, M
Document Type
Thesis or Dissertation
Date
2026-01-15
Date Accepted
Abstract
Introduction:
Myeloid cells are increasingly being recognised as playing a key role in antitumour
adaptive immunity, rather than their previously thought, over simplified
role in innate immunity. Programmed cell death ligand 1 (PD-L1) has recently
been shown to be expressed on myeloid subsets such as neutrophils and
monocytes, raising questions over the subsequent implications in immune
suppression and immune checkpoint inhibitor (ICI) efficacy. This thesis presents
an exploratory, multi-modal analysis of myeloid checkpoint expression in the
context of cancer immunotherapy, with a particular focus on PD-L1 expression
across both peripheral blood and intra-tumoural compartments.
Methods:
Combining multiparametric flow cytometry, longitudinal sampling and multiplex
immunohistochemistry (mIHC), we conducted an exploratory analysis
investigating the role of PD-L1+ neutrophils and monocytes (PD-L1+NM) in
both the peripheral blood and tumour microenvironment (TME) of patients with
skin and renal cancers undergoing immunotherapies. Patients were assessed
across cohorts including ICI and tumour infiltrating lymphocyte (TIL) therapies.
Additional myeloid markers LOX-1, VISTA and CXCR2 were investigated for
deeper phenotypic profiling. T cell subset correlation and high dimensional
clustering were performed to identify dynamic longitudinal changes.
Results:
PD-L1+NM were elevated in patients with cancers compared to controls and
increased during periods of systemic inflammation and immune-related adverse
events. Peripheral blood myeloid and T cell compartments revealed a
significant correlation between T cell activation and PD-L1+NM post ICI and TIL
infusion. Peripheral blood PD-L1+NM findings were not found to correlate well
with TME myeloid infiltrate. Finally, LOX-1+ polymorphonucler myeloid derived
suppressor cells (PNM-MDSC’s) were enriched in the periphery post TIL
lymphodepletion, and within the TME at baseline.
Citation
2026
DOI
Source Title
Publisher
Institute of Cancer Research (University Of London)
ISSN
eISSN
Collections
Research Team
Cell Ther Transl Immunol