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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2019

01-08-2019 | Translational Research and Biomarkers

A Combination of Positive Tumor HLA-I and Negative PD-L1 Expression Provides an Immune Rejection Mechanism in Bladder Cancer

Authors: José Francisco Flores-Martín, MD, Francisco Perea, PhD, Manuela Exposito-Ruiz, PhD, Francisco Javier Carretero, PhD, Teresa Rodriguez, PhD, Marina Villamediana, MS, Francisco Ruiz-Cabello, PhD, Federico Garrido, MD, PhD, José Manuel Cózar-Olmo, MD, PhD, Natalia Aptsiauri, MD, PhD

Published in: Annals of Surgical Oncology | Issue 8/2019

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Abstract

Background

Tumor human leukocyte antigen class I (HLA-I) expression plays an important role in T cell-mediated tumor rejection. Loss of HLA-I is associated with cancer progression and resistance to immunotherapy, including antibodies blocking programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling. Our objective was to analyze a correlation between HLA-I, tumor immune infiltration, and PD-L1/PD-1 axis in bladder cancer in association with the clinicopathologic features of patients.

Methods

We analyzed 85 cryopreserved bladder tumors by immunohistochemistry to investigate the expression of HLA-I, PD-L1, PD-1, CD3, CD8, and CXC chemokine receptor 4 (CXCR4). The results were correlated with tumor stage and other clinicopathologic variables of patients.

Results

We found a strong positive correlation between tumor HLA-I expression and infiltration with CD3+ and CD8 + T cells. PD-L1 expression was positive in 15.5% of tumors and heterogeneous in 40.5%, and was linked to a more advanced tumor stage. The majority of HLA-I-positive/heterogeneous tumors also expressed PD-L1 and PD-1, which were significantly correlated with each other and with lymphocyte infiltration. Interestingly, the analysis of the simultaneous expression of both markers revealed that 85.2% of tumors with a positive/heterogeneous HLA-I phenotype and negative for PD-L1 were mostly non-invasive, representing a ‘tumor rejection’ immune phenotype.

Conclusions

High tumor HLA-I expression with absence of PD-L1 provides bladder cancer with an immune rejection mechanism. Evaluation of PD-L1 and HLA-I together should be considered in bladder cancer and may provide a new predictive biomarker of tumor invasiveness and of the response to ‘immune checkpoint’ therapy.
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Metadata
Title
A Combination of Positive Tumor HLA-I and Negative PD-L1 Expression Provides an Immune Rejection Mechanism in Bladder Cancer
Authors
José Francisco Flores-Martín, MD
Francisco Perea, PhD
Manuela Exposito-Ruiz, PhD
Francisco Javier Carretero, PhD
Teresa Rodriguez, PhD
Marina Villamediana, MS
Francisco Ruiz-Cabello, PhD
Federico Garrido, MD, PhD
José Manuel Cózar-Olmo, MD, PhD
Natalia Aptsiauri, MD, PhD
Publication date
01-08-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 8/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07371-2

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