Michael Coston
Editor, Senior Moderator
Front. Immunology: Thymidine phosphorylase promotes SARS-CoV-2 spike protein-driven lung tumor development
#19,117
While the world continues to treat COVID as if it is now a mild illness, over the past 6 years we've seen compelling evidence that repeated COVID infections can seriously affect one's health (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection), along with a long litany of post-COVID sequelae.
A few (of many) recent studies include:
Nature Comms: The Risk of Kidney Disease Increases Following SARS-CoV-2 Infection Compared to influenza
EID Journal: Thrombotic Events and Stroke in the Year After COVID-19 or Other Acute Respiratory Infection
It may take years to fully parse out the long-term health impacts of COVID on society, but some researchers have expressed concerns over increased lung cancer risks due to SARS-CoV-2 infection (see 2022's SARS-CoV-2 and probable lung cancer risk).
While it wasn't limited to COVID, last year in Nature: Respiratory Viral Infections Awaken Metastatic Breast Cancer Cells in Lungs, we saw a study in mice that demonstrate that common respiratory viruses may awaken dormant cancer cells. The authors wrote:
Studies have shown that cancer metastasis can be triggered by inflammation. Infection by respiratory viruses, such as influenza and SARS-CoV-2, often causes inflammation.
Last last year, Molecular Aspects of Medicine published The double-edged sword: How SARS-CoV-2 might fuel lung cancer, which suggested that Post-COVID-19 pulmonary fibrosis could be a precursor to lung cancer.
Which brings us to a new study, which also suggests a potential link between COVID infection and an increased risk of lung cancer. First the Abstract, followed by some excerpts from a press release.
Thymidine phosphorylase promotes SARS-CoV-2 spike protein-driven lung tumor development
Cayleigh Wallace 1†, Alex Gileles-Hillel 2†, Amelia Cox 1,,David Gozal 1,3, , Wei Li 1*, Hong Yue 1*
(Continue . . . )
Researchers explore potential link between COVID-19 and lung cancer risk
Marshall University Joan C. Edwards School of Medicine
New findings from researchers at the Marshall University Joan C. Edwards School of Medicine and The Hebrew University of Jerusalem have identified a potential association between COVID-19 and increased lung cancer risk, driven by underlying biological mechanisms in the lung.
The study, published in Frontiers in Immunology, integrates human clinical data with mechanistic research in animal and cellular models to better understand how SARS-CoV-2, the virus that causes COVID-19, may contribute to long-term lung disease.
“Our findings suggest that COVID-19 may do more than cause acute illness—it may also create biological conditions in the lung that could contribute to increased cancer risk over time,” said Wei Li, Ph.D., professor of biomedical sciences at the Joan C. Edwards School of Medicine and co-corresponding author on the study. “Understanding these pathways is critical as we continue to study the long-term health impacts of the virus.”
The study identified a key role for thymidine phosphorylase (TYMP), a protein that may interact with the SARS-CoV-2 spike protein to promote inflammation, fibrosis and tumor-related pathways in the lung. Researchers found that this interaction may activate processes associated with cancer growth and alter the lung’s immune environment in ways that could support tumor formation.
(Continue . . .)
While there is growing circumstantial evidence that COVID may promote tumor-promoting environments, we still lack causal proof. That may come in time, but even without it, we've pretty good evidence that repeated COVID infections are best avoided if at all possible.
https://afludiary.blogspot.com/2026/04/front-immunology-thymidine.html
#19,117
While the world continues to treat COVID as if it is now a mild illness, over the past 6 years we've seen compelling evidence that repeated COVID infections can seriously affect one's health (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection), along with a long litany of post-COVID sequelae.
A few (of many) recent studies include:
Nature Comms: The Risk of Kidney Disease Increases Following SARS-CoV-2 Infection Compared to influenza
EID Journal: Thrombotic Events and Stroke in the Year After COVID-19 or Other Acute Respiratory Infection
It may take years to fully parse out the long-term health impacts of COVID on society, but some researchers have expressed concerns over increased lung cancer risks due to SARS-CoV-2 infection (see 2022's SARS-CoV-2 and probable lung cancer risk).
While it wasn't limited to COVID, last year in Nature: Respiratory Viral Infections Awaken Metastatic Breast Cancer Cells in Lungs, we saw a study in mice that demonstrate that common respiratory viruses may awaken dormant cancer cells. The authors wrote:
Studies have shown that cancer metastasis can be triggered by inflammation. Infection by respiratory viruses, such as influenza and SARS-CoV-2, often causes inflammation.
Last last year, Molecular Aspects of Medicine published The double-edged sword: How SARS-CoV-2 might fuel lung cancer, which suggested that Post-COVID-19 pulmonary fibrosis could be a precursor to lung cancer.
While we aren't at the point where we can say with any certainty that COVID infection causes cancer, researchers continue to find plausible reasons why it may create conditions that exacerbate the risks.
Which brings us to a new study, which also suggests a potential link between COVID infection and an increased risk of lung cancer. First the Abstract, followed by some excerpts from a press release.
Thymidine phosphorylase promotes SARS-CoV-2 spike protein-driven lung tumor development
Cayleigh Wallace 1†, Alex Gileles-Hillel 2†, Amelia Cox 1,,David Gozal 1,3, , Wei Li 1*, Hong Yue 1*
Abstract
Background:
COVID-19 survivors exhibit increased interstitial lung fibrosis, a known risk factor for lung cancer. We investigated whether SARS-CoV-2 spike protein (SP)-induced lung injury and elevated thymidine phosphorylase (TYMP) promote lung tumorigenesis.
Methods:
A TriNetX retrospective cohort analysis was combined with mechanistic studies in K18-hACE2TG and K18-hACE2TG/Tymp–/– mice. Mice received intratracheal SP or control lysate followed by a urethane-induced lung cancer protocol. Lung injury, inflammation, thrombosis, fibrosis, STAT3 activation, cytokine profiles, and tumor burden were assessed. In vitro assays evaluated SP- and RBD-induced ACE2 processing.
Results:
Propensity score-matched TriNetX cohorts demonstrated an increased lung cancer risk after COVID-19, particularly among current smokers (n = 166,807; RR 1.22; HR 1.50; P<.001). In mice, SP induced acute lung injury, neutrophil infiltration, and microthrombi, which were reduced in TYMP-deficient mice. SP markedly increased lung tumor incidence and aggressiveness, whereas TYMP deficiency reduced tumor formation from 50% to 18% of lung lobes. SP-induced STAT3 upregulation and collagen deposition were significantly attenuated in K18-hACE2TG/Tymp–/– mice. Cytokine profiling revealed a tumor-promoting, myeloid-dominant inflammatory milieu in K18-hACE2TG mice, in contrast to a T cell-inflamed, anti-tumor profile in K18-hACE2TG/Tymp–/– mice. SP and RBD altered ACE2 processing, generating lower-molecular-weight fragments consistent with enhanced turnover.
Conclusions:
SARS-CoV-2 SP drives lung injury, fibrosis, and tumorigenesis through a TYMP-dependent mechanism involving STAT3 signaling and inflammatory microenvironment remodeling. COVID-19 significantly increases lung cancer risk, especially in current smokers. TYMP represents a potential therapeutic target to mitigate long-term pulmonary consequences of COVID-19.
Background:
COVID-19 survivors exhibit increased interstitial lung fibrosis, a known risk factor for lung cancer. We investigated whether SARS-CoV-2 spike protein (SP)-induced lung injury and elevated thymidine phosphorylase (TYMP) promote lung tumorigenesis.
Methods:
A TriNetX retrospective cohort analysis was combined with mechanistic studies in K18-hACE2TG and K18-hACE2TG/Tymp–/– mice. Mice received intratracheal SP or control lysate followed by a urethane-induced lung cancer protocol. Lung injury, inflammation, thrombosis, fibrosis, STAT3 activation, cytokine profiles, and tumor burden were assessed. In vitro assays evaluated SP- and RBD-induced ACE2 processing.
Results:
Propensity score-matched TriNetX cohorts demonstrated an increased lung cancer risk after COVID-19, particularly among current smokers (n = 166,807; RR 1.22; HR 1.50; P<.001). In mice, SP induced acute lung injury, neutrophil infiltration, and microthrombi, which were reduced in TYMP-deficient mice. SP markedly increased lung tumor incidence and aggressiveness, whereas TYMP deficiency reduced tumor formation from 50% to 18% of lung lobes. SP-induced STAT3 upregulation and collagen deposition were significantly attenuated in K18-hACE2TG/Tymp–/– mice. Cytokine profiling revealed a tumor-promoting, myeloid-dominant inflammatory milieu in K18-hACE2TG mice, in contrast to a T cell-inflamed, anti-tumor profile in K18-hACE2TG/Tymp–/– mice. SP and RBD altered ACE2 processing, generating lower-molecular-weight fragments consistent with enhanced turnover.
Conclusions:
SARS-CoV-2 SP drives lung injury, fibrosis, and tumorigenesis through a TYMP-dependent mechanism involving STAT3 signaling and inflammatory microenvironment remodeling. COVID-19 significantly increases lung cancer risk, especially in current smokers. TYMP represents a potential therapeutic target to mitigate long-term pulmonary consequences of COVID-19.
(Continue . . . )
Researchers explore potential link between COVID-19 and lung cancer risk
Marshall University Joan C. Edwards School of Medicine
New findings from researchers at the Marshall University Joan C. Edwards School of Medicine and The Hebrew University of Jerusalem have identified a potential association between COVID-19 and increased lung cancer risk, driven by underlying biological mechanisms in the lung.
The study, published in Frontiers in Immunology, integrates human clinical data with mechanistic research in animal and cellular models to better understand how SARS-CoV-2, the virus that causes COVID-19, may contribute to long-term lung disease.
“Our findings suggest that COVID-19 may do more than cause acute illness—it may also create biological conditions in the lung that could contribute to increased cancer risk over time,” said Wei Li, Ph.D., professor of biomedical sciences at the Joan C. Edwards School of Medicine and co-corresponding author on the study. “Understanding these pathways is critical as we continue to study the long-term health impacts of the virus.”
The study identified a key role for thymidine phosphorylase (TYMP), a protein that may interact with the SARS-CoV-2 spike protein to promote inflammation, fibrosis and tumor-related pathways in the lung. Researchers found that this interaction may activate processes associated with cancer growth and alter the lung’s immune environment in ways that could support tumor formation.
(Continue . . .)
While there is growing circumstantial evidence that COVID may promote tumor-promoting environments, we still lack causal proof. That may come in time, but even without it, we've pretty good evidence that repeated COVID infections are best avoided if at all possible.
https://afludiary.blogspot.com/2026/04/front-immunology-thymidine.html