Bibliographic Details
| Title: |
Comorbidity between lung cancer and COVID-19 pneumonia: role of immunoregulatory gene transcripts in high -expressing normal lung |
| Authors: |
Vladimir Lazar, Jacques Raynaud, Shai Magidi, Catherine Bresson, Jean-François Martini, Susan Galbraith, Fanny Wunder, Amir Onn, Gerald Batist, Nicolas Girard, Ulrik Lassen, C. S. Pramesh, Amal Al-Omari, Sadakatsu Ikeda, Guy Berchem, Jean-Yves Blay, Benjamin Solomon, Enriqueta Felip, Josep Tabernero, Eitan Rubin, Thierry Philip, Angel Porgador, Ioana Berindan-Neagoe, Richard L. Schilsky, Razelle Kurzrock |
| Source: |
Therapeutic Advances in Medical Oncology, Vol 14 (2022) |
| Publisher Information: |
SAGE Publishing, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Background: SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 ( ACE2 , the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC). Methods: This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [ n = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial ( n = 32 metastatic NSCLC). Results: We identified patient subgroups with high and low ACE2 expression ( p = 1.55 × 10 −19 ) in normal lung tissue, presumed to be at higher and lower risk, respectively, of developing severe COVID-19 should they become infected. ACE2 transcript expression in normal lung tissues (but not in tumor tissue) of patients with NSCLC was higher in individuals with more advanced disease. High- ACE2 expressors had significantly higher levels of CD8+ cytotoxic T lymphocytes and natural killer cells but with presumably impaired function by high Thymocyte Selection-Associated High Mobility Group Box Protein TOX ( TOX ) expression. In addition, immune checkpoint-related molecules – PD-L1, CTLA-4, PD-1 , and TIGIT – are more highly expressed in normal (but not tumor) lung tissues; these molecules might dampen immune response to either viruses or cancer. Importantly, however, high inducible T-cell co-stimulator ( ICOS ), which can amplify immune and cytokine reactivity, significantly correlated with high ACE2 expression in univariable analysis of normal lung (but not lung tumor tissue). Conclusions: We report a normal lung immune-tolerant state that may explain a potential comorbidity risk between two diseases – NSCLC and susceptibility to COVID-19 pneumonia. Further, a NSCLC patient subgroup has normal lung tissue expressing high ACE2 and high ICOS transcripts, the latter potentially promoting a hyperimmune response, and possibly leading to severe COVID-19 pulmonary compromise. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1758-8359
17588359 |
| Relation: |
https://doaj.org/toc/1758-8359 |
| DOI: |
10.1177/17588359221133893 |
| Access URL: |
https://doaj.org/article/cacbf20affbf406896e87fc22d539ae7 |
| Accession Number: |
edsdoj.bf20affbf406896e87fc22d539ae7 |
| Database: |
Directory of Open Access Journals |
