Lívia Rojkó1, Lilla Reiniger2,3, Vanda Téglási2, Katalin Fábián4,5, Orsolya Pipek6, Attila Vágvölgyi7, László Agócs8, János Fillinger9,10, Zita Kajdácsi9, József Tímár11, Balázs Döme12,13, Zoltán Szállási3,14,15, Judit Moldvay16,17. 1. VI. Department of Pulmonology, National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, 1121, Hungary. 2. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, 1085, Hungary. 3. MTA-SE NAP, Brain Metastasis Research Group, 2nd Department of Pathology, Hungarian Academy of Sciences, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary. 4. Department of Pulmonology, Semmelweis University, Diósárok u. 1/C, Budapest, 1125, Hungary. 5. Department of Pathology, Szent Imre Teaching Hospital, Tétényi út 12-16, Budapest, 1115, Hungary. 6. Department of Physics of Complex Systems, Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, 1117, Hungary. 7. Department of Thoracic Surgery, National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, 1121, Hungary. 8. Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Ráth György u. 7-9, Budapest, 1122, Hungary. 9. Department of Pathology, National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, 1121, Hungary. 10. Department of Pathology, National Institute of Oncology, Ráth György u. 7-9, Budapest, 1122, Hungary. 11. 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary. 12. Department of Tumor Biology, National Korányi Institute of Pulmonology-Semmelweis University, Pihenő u. 1, Budapest, 1121, Hungary. 13. Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria. 14. Children's Hospital Informatics Program at the Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Harvard Medical School, A-111, 25 Shattuck St, Boston, MA, 02115, USA. 15. Department of Bio and Health Informatics, Technical University of Denmark, Anker Engelunds Vej 1 Bygning 101A, 2800, Kongens Lyngby, Denmark. 16. VI. Department of Pulmonology, National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, 1121, Hungary. drmoldvay@hotmail.com. 17. MTA-SE NAP, Brain Metastasis Research Group, 2nd Department of Pathology, Hungarian Academy of Sciences, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary. drmoldvay@hotmail.com.
Abstract
OBJECTIVES: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. MATERIALS AND METHODS: We determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy. RESULTS: PD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin-gemcitabine combination (p = 0.020), while in the carboplatin-paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy. CONCLUSIONS: This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.
OBJECTIVES: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. MATERIALS AND METHODS: We determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy. RESULTS:PD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin-gemcitabine combination (p = 0.020), while in the carboplatin-paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy. CONCLUSIONS: This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.
Authors: R Salgado; C Denkert; S Demaria; N Sirtaine; F Klauschen; G Pruneri; S Wienert; G Van den Eynden; F L Baehner; F Penault-Llorca; E A Perez; E A Thompson; W F Symmans; A L Richardson; J Brock; C Criscitiello; H Bailey; M Ignatiadis; G Floris; J Sparano; Z Kos; T Nielsen; D L Rimm; K H Allison; J S Reis-Filho; S Loibl; C Sotiriou; G Viale; S Badve; S Adams; K Willard-Gallo; S Loi Journal: Ann Oncol Date: 2014-09-11 Impact factor: 32.976
Authors: Ting-Yuan David Cheng; Susanna M Cramb; Peter D Baade; Danny R Youlden; Chukwumere Nwogu; Mary E Reid Journal: J Thorac Oncol Date: 2016-06-27 Impact factor: 15.609
Authors: Francesco Passiglia; Giuseppe Bronte; Viviana Bazan; Clara Natoli; Sergio Rizzo; Antonio Galvano; Angela Listì; Giuseppe Cicero; Christian Rolfo; Daniele Santini; Antonio Russo Journal: Oncotarget Date: 2016-04-12
Authors: D Gompelmann; K Sinn; J Brugger; D Bernitzky; B Mosleh; H Prosch; S Geleff; A Blessing; A Tiefenbacher; K Hoetzenecker; M Idzko; M A Hoda Journal: J Cancer Res Clin Oncol Date: 2022-06-16 Impact factor: 4.553
Authors: Daniel J Rubins; Xiangjun Meng; Paul McQuade; Michael Klimas; Krista Getty; Shu-An Lin; Brett M Connolly; Stacey S O'Malley; Hyking Haley; Mona Purcell; Liza Gantert; Marie Holahan; Joel Lindgren; Pär Eklund; Caroline Ekblad; Fredrik Y Frejd; Eric D Hostetler; Dinko E González Trotter; Jeffrey L Evelhoch Journal: Mol Imaging Biol Date: 2020-10-23 Impact factor: 3.488
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675