TY - JOUR
T1 - Comorbidity between lung cancer and COVID-19 pneumonia: role of immunoregulatory gene transcripts in high ACE2-expressing normal lung
AU - Lazar, V.
AU - Raynaud, J.
AU - Magidi, S.
AU - Bresson, C.
AU - Martini, J. F.
AU - Galbraith, S.
AU - Wunder, F.
AU - Onn, A.
AU - Batist, G.
AU - Girard, N.
AU - Lassen, U.
AU - Pramesh, C. S.
AU - Al-Omari, A.
AU - Ikeda, S.
AU - Berchem, G.
AU - Blay, J. Y.
AU - Solomon, B.
AU - Felip, E.
AU - Tabernero, J.
AU - Rubin, E.
AU - Philip, T.
AU - Porgador, A.
AU - Berindan-Neagoe, I.
AU - Schilsky, R. L.
AU - Kurzrock, R.
N1 - Funding: The consensus project was endorsed by the European Society
for Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA).
PY - 2022/10/28
Y1 - 2022/10/28
N2 - 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.
AB - 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.
UR - https://pubmed.ncbi.nlm.nih.gov/36324736
U2 - 10.1177/17588359221133893
DO - 10.1177/17588359221133893
M3 - Article
C2 - 36324736
SN - 1758-8359
VL - 14
JO - Therapeutic Advances in Medical Oncology
JF - Therapeutic Advances in Medical Oncology
M1 - 17588359221133893
ER -