| Title: |
Comorbidity between lung cancer and COVID-19 pneumonia: role of immunoregulatory gene transcripts in high ACE2-expressing normal lung |
| Authors: |
Lazar, V; Raynaud, J; Magidi, S; Bresson, C; Martini, JF; Galbraith, S; Wunder, F; Onn, A; Batist, G; Girard, N; Lassen, U; Pramesh, CS; Al-Omari, A; Ikeda, S; Berchem, G; Blay, JY; Solomon, B; Felip, E; Tabernero, J; Rubin, E; Philip, T; Porgador, A; Berindan-Neagoe, I; Schilsky, RL; Kurzrock, R |
| Publisher Information: |
SAGE Publications |
| Publication Year: |
2022 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1758-8340 |
| Relation: |
pii: 10.1177_17588359221133893; https://hdl.handle.net/11343/335483 |
| Availability: |
https://hdl.handle.net/11343/335483 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.839B2D60 |
| Database: |
BASE |