Lilla Reiniger1,2, Vanda Téglási1, Orsolya Pipek3, Lívia Rojkó4, Tibor Glasz5, Attila Vágvölgyi6, Ilona Kovalszky1, Márton Gyulai7, Zoltán Lohinai4, Erzsébet Rásó8, József Tímár8, Balázs Döme9,10, Zoltán Szállási2,11,12, Judit Moldvay2,9. 1. a 1st Department of Pathology and Experimental Cancer Research , Semmelweis University , Budapest , Hungary. 2. b 2nd Department of Pathology, MTA-SE NAP Brain Metastasis Research Group Hungarian Academy of Sciences , Semmelweis University , Budapest , Hungary. 3. c Department of Physics of Complex Systems , Eötvös Loránd University , Budapest , Hungary. 4. d VI. Department of Pulmonology , National Korányi Institute of Pulmonology , Budapest , Hungary. 5. e Department of Pathology , National Korányi Institute of Pulmonology , Budapest , Hungary. 6. f Department of Thoracic Surgery , National Korányi Institute of Pulmonology , Budapest , Hungary. 7. g 2nd Department of Pulmonology , County Hospital of Pulmonology , Törökbálint , Hungary. 8. h 2nd Department of Pathology , Semmelweis University , Budapest , Hungary. 9. i Department of Tumor Biology, National Korányi Institute of Pulmonology- Semmelweis University , Budapest , Hungary. 10. j Division of Thoracic Surgery, Comprehensive Cancer Center , Medical University of Vienna , Vienna , Austria. 11. k Division of Health Sciences and Technology, Children's Hospital Informatics Program at the Harvard-Massachusetts Institute of Technology , Harvard Medical School , Boston , MA , USA. 12. l Danish Cancer Society Research Center , Copenhagen , Denmark.
Abstract
Background: Predictive biomarkers for immunotherapy in lung cancer are intensively investigated; however, correlations between PD-L1/PD-1 expressions and clinical features or histopathological tumor characteristics determined on hematoxylin and eosin stained sections have not extensively been studied. Material and methods: We determined PD-L1 expression of tumor cells (TC) and immune cells (IC), and PD-1 expression of IC by immunohistochemistry in 268 lung adenocarcinoma (LADC) patients, and correlated the data with smoking, COPD, tumor grade, necrosis, lepidic growth pattern, vascular invasion, density of stromal IC, and EGFR/KRAS status of the tumors. Results: There was a positive correlation between PD-L1 expression of TC and IC, as well as PD-L1 and PD-1 expression of IC. Tumor necrosis was associated with higher PD-L1 expression of TC and PD-1 expression of IC. A negative correlation was observed between lepidic growth pattern and PD-L1 expression of TC and PD-L1/PD-1 expression of IC. EGFR mutation seemed to negatively correlate with PD-1 expression of IC, but this tendency could not be verified when applying corrections for multiple comparisons. No significant effect of the KRAS mutation on any of the studied variables could be established. Conclusion: Here we first demonstrate that the presence of necrosis correlates with higher PD-L1 expression of TC and PD-1 expression of IC in LADC. Further studies are required to determine the predictive value of this observation in LADC patients receiving immunotherapy.
Background: Predictive biomarkers for immunotherapy in lung cancer are intensively investigated; however, correlations between PD-L1/PD-1 expressions and clinical features or histopathological tumor characteristics determined on hematoxylin and eosin stained sections have not extensively been studied. Material and methods: We determined PD-L1 expression of tumor cells (TC) and immune cells (IC), and PD-1 expression of IC by immunohistochemistry in 268 lung adenocarcinoma (LADC) patients, and correlated the data with smoking, COPD, tumor grade, necrosis, lepidic growth pattern, vascular invasion, density of stromal IC, and EGFR/KRAS status of the tumors. Results: There was a positive correlation between PD-L1 expression of TC and IC, as well as PD-L1 and PD-1 expression of IC. Tumor necrosis was associated with higher PD-L1 expression of TC and PD-1 expression of IC. A negative correlation was observed between lepidic growth pattern and PD-L1 expression of TC and PD-L1/PD-1 expression of IC. EGFR mutation seemed to negatively correlate with PD-1 expression of IC, but this tendency could not be verified when applying corrections for multiple comparisons. No significant effect of the KRAS mutation on any of the studied variables could be established. Conclusion: Here we first demonstrate that the presence of necrosis correlates with higher PD-L1 expression of TC and PD-1 expression of IC in LADC. Further studies are required to determine the predictive value of this observation in LADC patients receiving immunotherapy.
Authors: Marclesson Alves; Daniela de Paula Borges; Aline Kimberly; Francisco Martins Neto; Ana Claudia Oliveira; Juliana Cordeiro de Sousa; Cleto D Nogueira; Benedito A Carneiro; Fabio Tavora Journal: Front Oncol Date: 2021-03-09 Impact factor: 6.244
Authors: James A Diao; Jason K Wang; Wan Fung Chui; Andrew H Beck; Hunter L Elliott; Amaro Taylor-Weiner; Victoria Mountain; Sai Chowdary Gullapally; Ramprakash Srinivasan; Richard N Mitchell; Benjamin Glass; Sara Hoffman; Sudha K Rao; Chirag Maheshwari; Abhik Lahiri; Aaditya Prakash; Ryan McLoughlin; Jennifer K Kerner; Murray B Resnick; Michael C Montalto; Aditya Khosla; Ilan N Wapinski Journal: Nat Commun Date: 2021-03-12 Impact factor: 14.919
Authors: Kristina Breitenecker; Monika Homolya; Andreea C Luca; Veronika Lang; Christoph Trenk; Georg Petroczi; Julian Mohrherr; Jaqueline Horvath; Stefan Moritsch; Lisa Haas; Margarita Kurnaeva; Robert Eferl; Dagmar Stoiber; Richard Moriggl; Martin Bilban; Anna C Obenauf; Christiane Ferran; Balazs Dome; Viktoria Laszlo; Balázs Győrffy; Katalin Dezso; Judit Moldvay; Emilio Casanova; Herwig P Moll Journal: Sci Transl Med Date: 2021-07-07 Impact factor: 17.956