Investigation of the effect of PD-L1 blockade on triple negative breast cancer cells using fourier transform infrared spectroscopy
| Autor: | Eyad Elkord, Salman M Toor, Mohamed H. M. Ali, Ehsan Ullah, Khalid Al-Saad, Prasanna R. Kolatkar, Kamal Mroue, Fazle Rakib, Raghvendra Mall |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
spectroscopy medicine.medical_treatment T cell Immunology tumor cells biochemical alterations lcsh:Medicine Tumor cells Article 03 medical and health sciences 0302 clinical medicine Immune system breast cancer Breast cancer Cancer immunotherapy Atezolizumab PD-L1 Drug Discovery medicine Pharmacology (medical) Chemometric analysis Triple-negative breast cancer Spectroscopy Cancer immunology Pharmacology biology Chemistry lcsh:R 030104 developmental biology Infectious Diseases medicine.anatomical_structure FTIR Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein chemometric analysis Biochemical alterations |
| Zdroj: | Vaccines, Vol 7, Iss 3, p 109 (2019) Vaccines Volume 7 Issue 3 |
| Popis: | 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 ?-helical structure to ?-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. - 2019 by the authors. Licensee MDPI, Basel, Switzerland. Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar Department of Chemistry and Earth Sciences, Qatar University (QU), P.O. Box 2713 Doha, Qatar Qatar Computing Research Institute, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar Qatar Environment & Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar Correspondence: mohamali@hbku.edu.qa (M.H.M.A.); eelkord@hbku.edu.qa (E.E.) Scopus |
| Databáze: | OpenAIRE |
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