Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy

Interactions between programmed death-1 (PD-1) with its ligand PD-L1 on tumor cells can antagonize T cell responses. Inhibiting these interactions using immune checkpoint inhibitors has shown promise in cancer immunotherapy. MDA-MB-231 is a triple negative breast cancer cell line that expresses PD-L...

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Main Authors: Mohamed H. M. Ali, Salman M Toor, Fazle Rakib, Raghvendra Mall, Ehsan Ullah, Kamal Mroue, Prasanna R. Kolatkar, Khalid Al-Saad, Eyad Elkord
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/7/3/109
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author Mohamed H. M. Ali
Salman M Toor
Fazle Rakib
Raghvendra Mall
Ehsan Ullah
Kamal Mroue
Prasanna R. Kolatkar
Khalid Al-Saad
Eyad Elkord
author_facet Mohamed H. M. Ali
Salman M Toor
Fazle Rakib
Raghvendra Mall
Ehsan Ullah
Kamal Mroue
Prasanna R. Kolatkar
Khalid Al-Saad
Eyad Elkord
author_sort Mohamed H. M. Ali
collection DOAJ
description Interactions between programmed death-1 (PD-1) with its ligand PD-L1 on tumor cells can antagonize T cell responses. Inhibiting these interactions using immune checkpoint inhibitors has shown promise in cancer immunotherapy. MDA-MB-231 is a triple negative breast cancer cell line that expresses PD-L1. In this study, we investigated the biochemical changes in MDA-MB-231 cells following treatment with atezolizumab, a specific PD-L1 blocker. Our readouts were Fourier Transform Infrared (FTIR) spectroscopy and flow cytometric analyses. Chemometrical analysis, such as principal component analysis (PCA), was applied to delineate the spectral differences. We were able to identify the chemical alterations in both protein and lipid structure of the treated cells. We found that there was a shift from random coil and α-helical structure to β-sheet conformation of PD-L1 on tumor cells due to atezolizumab treatment, which could hinder binding with its receptors on immune cells, ensuring sustained T cell activation for potent immune responses. This work provides novel information about the effects of atezolizumab at molecular and cellular levels. FTIR bio-spectroscopy, in combination with chemometric analyses, may expedite research and offer new approaches for cancer immunology.
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spelling doaj.art-dab869c910a84b7b9b332acfc19b6b5a2022-12-22T04:09:32ZengMDPI AGVaccines2076-393X2019-09-017310910.3390/vaccines7030109vaccines7030109Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared SpectroscopyMohamed H. M. Ali0Salman M Toor1Fazle Rakib2Raghvendra Mall3Ehsan Ullah4Kamal Mroue5Prasanna R. Kolatkar6Khalid Al-Saad7Eyad Elkord8Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, QatarCancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, QatarDepartment of Chemistry and Earth Sciences, Qatar University (QU), P.O. Box 2713 Doha, QatarQatar Computing Research Institute, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, QatarQatar Computing Research Institute, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, QatarQatar Environment & Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, QatarDiabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, QatarDepartment of Chemistry and Earth Sciences, Qatar University (QU), P.O. Box 2713 Doha, QatarCancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, QatarInteractions between programmed death-1 (PD-1) with its ligand PD-L1 on tumor cells can antagonize T cell responses. Inhibiting these interactions using immune checkpoint inhibitors has shown promise in cancer immunotherapy. MDA-MB-231 is a triple negative breast cancer cell line that expresses PD-L1. In this study, we investigated the biochemical changes in MDA-MB-231 cells following treatment with atezolizumab, a specific PD-L1 blocker. Our readouts were Fourier Transform Infrared (FTIR) spectroscopy and flow cytometric analyses. Chemometrical analysis, such as principal component analysis (PCA), was applied to delineate the spectral differences. We were able to identify the chemical alterations in both protein and lipid structure of the treated cells. We found that there was a shift from random coil and α-helical structure to β-sheet conformation of PD-L1 on tumor cells due to atezolizumab treatment, which could hinder binding with its receptors on immune cells, ensuring sustained T cell activation for potent immune responses. This work provides novel information about the effects of atezolizumab at molecular and cellular levels. FTIR bio-spectroscopy, in combination with chemometric analyses, may expedite research and offer new approaches for cancer immunology.https://www.mdpi.com/2076-393X/7/3/109breast cancertumor cellsspectroscopyFTIRbiochemical alterationschemometric analysis
spellingShingle Mohamed H. M. Ali
Salman M Toor
Fazle Rakib
Raghvendra Mall
Ehsan Ullah
Kamal Mroue
Prasanna R. Kolatkar
Khalid Al-Saad
Eyad Elkord
Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy
Vaccines
breast cancer
tumor cells
spectroscopy
FTIR
biochemical alterations
chemometric analysis
title Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy
title_full Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy
title_fullStr Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy
title_full_unstemmed Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy
title_short Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy
title_sort investigation of the effect of pd l1 blockade on triple negative breast cancer cells using fourier transform infrared spectroscopy
topic breast cancer
tumor cells
spectroscopy
FTIR
biochemical alterations
chemometric analysis
url https://www.mdpi.com/2076-393X/7/3/109
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