A Study on the Clinical Significance of Blood Exosomal PD-L1 in
                    Non-Small Cell Lung Cancer Patients and its Correlation with PD-L1 in Tumor
                    Tissues

Yonghong Cheng; Feiyun Chang; Yanmei Gong; Ping Lu

doi:10.1055/a-2110-7497

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2023; 55(11): 788-793
DOI: 10.1055/a-2110-7497

Original Article: Endocrine Research

A Study on the Clinical Significance of Blood Exosomal PD-L1 in Non-Small Cell Lung Cancer Patients and its Correlation with PD-L1 in Tumor Tissues

Authors

Yonghong Cheng

¹Department of Oncology, Shanxi Jishan County People’s Hospital, Yuncheng, China
Feiyun Chang

²Department of Thoracic Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
Yanmei Gong

³Department of Oncology, Shanxi Yuncheng Center Hospital, Yuncheng, China
Ping Lu

⁴Department of Radiotherapy Head and Neck Comprehensive Ward, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China

Abstract

Exosomal programmed cell-death ligand 1 (ePD-L1) can influence immune inhibition and dysfunction. We were dedicated to unearthing the relation between ePD-L1 in blood and pathological characteristics as well as PD-L1 in tumor tissues. We recruited 65 non-small cell lung cancer (NSCLC) patients for exosome extraction and detected the blood ePD-L1 expression in these patients by enzyme-linked immunosorbent assay (ELISA) method. Besides, the correlation between blood ePD-L1 and patients’ pathological characteristics was also analyzed. The expression of PD-L1 in tumor tissues was tested by immunohistochemistry (IHC) and its correlation with blood ePD-L1 expression level was analyzed by Spearman correlation coefficient. No significant correlation was observed in PD-L1 expression levels between blood-derived exosome and tumor tissue. Altogether, high blood ePD-L1 expression was relevant to NSCLC progression, while no such relevance to PD-L1 expression in tumor tissue.

Key words

NSCLC - exosomes - PD-L1 - immunotherapy, immunity

Full Text

References

References
1 Oberndorfer F, Mullauer L. Molecular pathology of lung cancer: current status and perspectives. Curr Opin Oncol 2018; 30: 69-76
2 Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest 2015; 125: 3384-3391
3 Topalian SL, Taube JM, Anders RA. et al. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 2016; 16: 275-287
4 Ribas A, Hamid O, Daud A. et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 2016; 315: 1600-1609
5 Liede A, Hernandez RK, Wade SW. et al. An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer. Oncoimmunology 2018; 7: e1480301
6 Lemjabbar-Alaoui H, Hassan OU, Yang YW. et al. Lung cancer: Biology and treatment options. Biochim Biophys Acta 2015; 1856: 189-210
7 Chen Y, Liu Q, Chen Z. et al. PD-L1 expression and tumor mutational burden status for prediction of response to chemotherapy and targeted therapy in non-small cell lung cancer. J Exp Clin Cancer Res 2019; 38: 193
8 Incorvaia L, Fanale D, Badalamenti G. et al. Programmed death ligand 1 (PD-L1) as a predictive biomarker for pembrolizumab therapy in patients with aadvanced non-small-cell lung cancer (NSCLC). Adv Ther 2019; 36: 2600-2617
9 Patel SP, Kurzrock R. PD-L1 Expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 2015; 14: 847-856
10 Payandeh Z, Khalili S, Somi MH. et al. PD-1/PD-L1-dependent immune response in colorectal cancer. J Cell Physiol 2020; 235: 5461-5475
11 Oliveira AF, Bretes L, Furtado I. Review of PD-1/PD-L1 Inhibitors in metastatic dMMR/MSI-H colorectal cancer. Front Oncol 2019; 9: 396
12 Goodman AM, Kato S, Bazhenova L. et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther 2017; 16: 2598-2608
13 Darvin P, Toor SM, Sasidharan Nair V. et al. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med 2018; 50: 111
14 Nixon AB, Schalper KA, Jacobs I. et al. Peripheral immune-based biomarkers in cancer immunotherapy: can we realize their predictive potential?. J Immunother Cancer 2019; 7: 325
15 Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol 2016; 17: e542-e551
16 Garcia-Diaz A, Shin DS, Moreno BH. et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep 2017; 19: 1189-1201
17 Reck M, Rodriguez-Abreu D, Robinson AG. et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375: 1823-1833
18 Garon EB, Rizvi NA, Hui R. et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372: 2018-2028
19 Li C, Li C, Zhi C. et al. Clinical significance of PD-L1 expression in serum-derived exosomes in NSCLC patients. J Transl Med 2019; 17: 355
20 Whiteside TL. Exosomes and tumor-mediated immune suppression. J Clin Invest 2016; 126: 1216-1223
21 Guay C, Regazzi R. Exosomes as new players in metabolic organ cross-talk. Diabetes Obes Metab 2017; 19: 137-146
22 Li Y, Zheng Q, Bao C. et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 2015; 25: 981-984
23 Melo SA, Luecke LB, Kahlert C. et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015; 523: 177-182
24 Tang MK, Wong AS. Exosomes: Emerging biomarkers and targets for ovarian cancer. Cancer Lett 2015; 367: 26-33
25 Chen G, Huang AC, Zhang W. et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2018; 560: 382-386
26 Theodoraki MN, Yerneni SS, Hoffmann TK. et al. Clinical significance of PD-L1(+) exosomes in plasma of head and neck cancer patients. Clin Cancer Res 2018; 24: 896-905
27 Theodoraki MN, Yerneni S, Gooding WE. et al. Circulating exosomes measure responses to therapy in head and neck cancer patients treated with cetuximab, ipilimumab, and IMRT. Oncoimmunology 2019; 8: 1593805
28 Cordonnier M, Nardin C, Chanteloup G. et al. Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients. J Extracell Vesicles 2020; 9: 1710899
29 Belkin AN, Freynd GG. [A new one in the lung and pleura neoplasms classification (WHO, 2021, 5th edition)]. Ark Patol 2022; 84: 28-34
30 Mathieu M, Névo N, Jouve M. et al. Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9. Nat Commun 2021; 12: 4389
31 de Ruiter EJ, Mulder FJ, Koomen BM. et al. Comparison of three PD-L1 immunohistochemical assays in head and neck squamous cell carcinoma (HNSCC). Modern Pathol 2021; 34: 1125-1132
32 Xia B, Herbst RS. Immune checkpoint therapy for non-small-cell lung cancer: an update. Immunotherapy 2016; 8: 279-298
33 Vokes EE, Ready N, Felip E. et al. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol 2018; 29: 959-965
34 Herbst RS, Giaccone G, de Marinis F. et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med 2020; 383: 1328-1339
35 Becker A, Thakur BK, Weiss JM. et al. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell 2016; 30: 836-848
36 Poggio M, Hu T, Pai CC. et al. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell 2019; 177: 414-427.e413
37 Fan Y, Che X, Qu J. et al. Exosomal PD-L1 retains immunosuppressive activity and is associated with gastric cancer prognosis. Ann Surg Oncol 2019; 26: 3745-3755

Supplementary Material

Supplementary Material (PDF) (opens in new window)