Skip to content

Advertisement

  • Poster presentation
  • Open Access

PD-L1 and MHC-I expression in 19 human tumor cell lines and modulation by interferon-gamma treatment

  • Italia Grenga1,
  • Renee N Donahue2,
  • Lauren Lepone1,
  • Jessa Bame1,
  • Jeffrey Schlom1 and
  • Benedetto Farsaci1
Journal for ImmunoTherapy of Cancer20142(Suppl 3):P102

https://doi.org/10.1186/2051-1426-2-S3-P102

Published: 6 November 2014

Keywords

Tumor MicroenvironmentSurface ExpressionInterferon GammaAdoptive TransferHuman Tumor Cell Line

Background

The aim of this study was to analyze the expression of PD-L1 and MHC-I in 19 human tumor cell lines and changes after interferon gamma (IFN-γ) treatment, in order to evaluate the potentiality of combining anti-PD-L1 antibody with other immunotherapies.

Methods

Nineteen human tumor cell lines were cultured according with ATCC guidelines: 5 colon (Caco-2, SW620, SW480, Colo-205 and HT-29), 4 ovarian (OV-17, OVCAR-3, ES-2, SKOV-3), 3 breast (MDA-MB-231, MCF-7, ZR-75), 3 lung (H441, H1703, H460), 2 prostate (LnCap and PC-3), and 2 pancreatic (CFPAC-1 and ASPC-1). Cells were analyzed by flow-cytometry for PD-L1 (clone 29E.2A3) and MHC-I expression. The surface expression of PD-L1 was considered as low, medium, or high based on the percentage of positive cells (80%, respectively). Cells were also analyzed for PD-L1 mRNA expression by RT-PCR. Experiments were performed with or without IFN-γ pre-treatment (10 ng/ml, 24 hours).

Results

The expression of PD-L1 was as follows. Low: 4/5 colon (SW620, SW480, Colo-205 and HT-29), 1/4 ovarian (OVCAR-3), 2/3 breast (ZR-75, MCF-7), and 1/2 pancreatic (ASPC-1). Medium: 1/5 colon (Caco-2), 2/4 ovarian (OV-17, SKOV-3), 2/3 lung (H460, H1703), and 1/2 prostate (LnCap). High: 1/4 ovarian (ES-2), 1/3 lung (H441), and 1/2 prostate (PC-3), 1/3 breast (MDA-MB-231), and 1/2 pancreatic (ASPC-1). After IFN-γ pre-treatment, 14/19 cell lines showed a >50% increase of PD-L1 and 14/19 a >50% increase of MHC-I (either percentage positive or MFI). In 13/19 cell lines both markers increased. IFN-γ pre-treatment caused an increase >100% of PD-L1 mRNA expression in 14/19 cell lines. CFPAC-1 (pancreatic) showed an increase of surface PD-L1 without mRNA change; on the opposite, H1703 (lung) showed mRNA increase without changes in surface expression.

Conclusions

Tumor cells express different percentage of PD-L1 and MHC-I in their surface. In most of the cells analyzed, both molecules are increased by exposure to IFN-γ. Based on these observations, immunotherapies aiming to increase IFN-γ in the tumor microenvironment, such as therapeutic vaccines or T cell adoptive transfer, can facilitate immune recognition of tumor cells by an increase of MHC-I on the surface of tumor cells. On the other hand, the increased PD-L1 expression in the tumor can be an ideal target for anti-PD-L1 antibody treatment.

Authors’ Affiliations

(1)
Laboratory of Tumor Immunology and Biology, CCR, NCI, NIH, Bethesda, USA
(2)
NCI/CCR/LTIB, Bethesda, USA

Copyright

© Grenga et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement