The strongest association was observed for PM₂.₅, the microscopic particles measuring 2.5 micrometres or less in diameter. Because these particles are so small, they can penetrate deep into the lungs and, in some cases, cross into the bloodstream. Their chemical composition varies according to their source, but PM₂.₅ may contain metals, soot, organic compounds and other substances capable of triggering oxidative stress and chronic inflammation. Over time, these biological disturbances can damage DNA, alter immune responses and interfere with normal cellular repair. The new analysis found that every additional 10 micrograms of PM₂.₅ per cubic metre of air was associated with a 16.0 percent increase in the risk of all cancers combined.

The study also identified a J-shaped exposure–response relationship for PM₂.₅. In epidemiology, this pattern indicates that the risk does not rise in a simple straight line across all exposure levels. At lower concentrations, changes in risk may be relatively modest or difficult to distinguish, while at higher concentrations the curve turns upward more sharply. A J-shaped association can reflect biological thresholds, differences in population susceptibility or the effects of particularly intense pollution exposure. It may also emerge when background risks and other environmental factors vary across locations. The researchers used statistical models designed to capture this type of nonlinear pattern rather than assuming that every incremental increase in pollution carries exactly the same effect.

Ozone, commonly known as O₃, showed a different pattern. Unlike the protective ozone layer high in the atmosphere, ground-level ozone is a harmful pollutant formed when nitrogen oxides and volatile organic compounds react in sunlight. It is often more severe during hot, sunny conditions and can travel across administrative boundaries, making it difficult for individual cities to control. Ozone irritates the airways and can promote inflammation throughout the respiratory system. According to the study, each 10 micrograms per cubic metre increase in long-term ozone exposure was associated with a 4.23 percent rise in the risk of all cancers. The relationship was described as near-linear, meaning that the estimated risk increased more steadily as exposure rose.

Nitrogen dioxide, or NO₂, was associated with an 11.7 percent increase in all-cancer risk for every 10 micrograms per cubic metre increase in long-term exposure. The gas is generated primarily by fuel combustion, especially from vehicles, power plants and industrial activity. It can damage airway tissues directly and also contributes to the formation of ozone and secondary particles. Nitrogen dioxide is therefore both a pollutant in its own right and part of a wider atmospheric chemical system. Exposure is frequently highest near busy roads and in densely populated urban areas, where traffic emissions can create sharp differences in air quality from one neighbourhood to another.

When the researchers translated these relative risks into population-level estimates, the scale of the findings became considerably larger. PM₂.₅ exposure was estimated to be associated with approximately 8.82 million incident cancer cases worldwide during the study period. Ozone was linked to about 2.59 million cases, while nitrogen dioxide was associated with approximately 6.67 million cases. These figures represent attributable burdens calculated from population exposure and estimated risk relationships; they do not mean that every individual case can be traced to a single pollutant. Cancer is a multifactorial disease influenced by age, genetics, smoking, alcohol use, infections, diet, occupational hazards and access to medical care. Nevertheless, even a modest increase in risk can produce a substantial number of cases when it affects billions of people.

The researchers used distributed lag non-linear models, a method that can evaluate both delayed effects and nonlinear exposure patterns. Cancer often develops over years or decades, so the consequences of an exposure may not appear immediately after pollution levels rise. Distributed lag models allow investigators to examine how risk may accumulate across time rather than assigning all effects to the moment of exposure. The approach can also account for changing exposure levels, differences between locations and potential variations in the time required for environmental damage to contribute to disease. By combining these models with global cancer and pollution data, the study aimed to estimate not only relative risks but also the number of cases potentially linked to ambient air pollution.

One of the study’s most striking observations was the consistently higher attributable risk and burden among women for most malignancies. The analysis does not establish a single explanation for this difference, and the causes may vary by region and cancer type. Women and men can experience different occupational and household exposures, including pollution from cooking fuels, heating systems and poorly ventilated indoor environments. Biological differences in hormone regulation, immune function, body composition and pollutant metabolism could also influence susceptibility. In addition, patterns of healthcare access, diagnosis and cancer registration may affect the data. The finding highlights the importance of examining air pollution through a sex-specific lens rather than assuming that the same exposure produces identical outcomes in every population.

The results arrive as cities worldwide confront overlapping challenges from traffic emissions, industrial pollution, wildfires and climate-driven heat extremes. Fine particles can travel long distances, while hot weather can intensify ozone formation and increase the frequency of stagnant-air episodes. Reducing fossil-fuel combustion, improving public transport, tightening industrial standards, expanding clean household energy and monitoring pollution at neighbourhood scale could therefore deliver benefits beyond cardiovascular and respiratory health. The authors describe their estimates as an impetus for stronger public-health policies aimed at reducing the global cancer burden. Although the study is observational and its estimates depend on the quality of exposure data, cancer records and statistical assumptions, its vast geographic scope underscores a central message: cleaner air may be one of the most consequential cancer-prevention measures available to governments and communities.

Subject of Research: Global cancer burden associated with long-term exposure to ambient air pollution

Article Title: Global cancer burden associated with long-term exposure to ambient air pollution

Article References: Zhang, G., Li, Y., Li, A. et al. Global cancer burden associated with long-term exposure to ambient air pollution. Nat. Health (2026). https://doi.org/10.1038/s44360-026-00180-4

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s44360-026-00180-4

Keywords: Air pollution, PM₂.₅, ozone, nitrogen dioxide, cancer, public health, environmental epidemiology, global health, attributable burden

The hormone, thymulin, is produced by the thymus, a small immune organ located behind the breastbone. The thymus is best known for supporting the development and education of T cells, the immune cells that recognize infected or abnormal cells. Its activity declines substantially with age, a process called thymic involution. According to the USC team, thymulin levels fall alongside this structural and functional decline, while inflammatory signals rise. The researchers propose that this hormonal loss may influence the immune system far beyond T-cell production, affecting the broader inflammatory environment in which cancer develops and responds to treatment.

In a study published in Nature Communications, the scientists reported that restoring thymulin reduced inflammation and improved survival in older mice with cancer. The hormone also made immunotherapy more effective in these animals. The work is significant because it moved beyond an association between an aging thymus and inflammation, identifying a causal chain in which reduced thymulin activity contributes to an inflammatory state that can accelerate cancer progression and interfere with immune-based treatment. The findings provide a possible explanation for why many older patients respond differently to immunotherapy than younger individuals.

“Scientists have traditionally viewed the aging thymus as important mainly because of its effects on one part of the immune system—T cells,” said Fumito Ito, MD, PhD, professor of surgery and immunology and immune therapeutics at the Keck School of Medicine and principal investigator of the research. “Our findings suggest its influence is much broader, helping regulate chronic inflammation in ways that affect cancer.” The new grant will allow the team to examine how thymulin communicates with immune cells and whether that communication can be converted into a treatment strategy.

The first phase of the project will focus on the molecular mechanisms behind thymulin’s anti-inflammatory effects. Researchers will study immune cells in living mice as well as human immune cells in laboratory experiments. They plan to map the signaling pathways activated by thymulin and identify the genes whose activity changes after exposure to the hormone. These experiments could reveal whether thymulin acts directly on immune cells, alters the production of inflammatory molecules or reshapes communication among several cell types. Understanding these steps will be essential for determining how the hormone might be used safely in humans.

The researchers will then investigate how thymulin changes the tumor microenvironment, the complex network of cancer cells, immune cells, blood vessels and signaling molecules surrounding a tumor. Many cancers suppress immune activity by creating an environment that prevents T cells from entering the tumor or stops them from killing malignant cells. In aged mice with breast cancer or melanoma that respond poorly to immunotherapy, the team will test whether thymulin can reverse some of these effects. A central question is whether the hormone generates new anti-cancer immune responses, strengthens immune attacks that already exist, or performs both functions.

The project will also examine thymulin’s potential against metastatic disease. Metastasis occurs when cancer cells leave the original tumor, travel through the bloodstream or lymphatic system and establish tumors in distant organs. These secondary tumors are responsible for most cancer-related deaths and are often difficult to treat with immunotherapy alone. Ito’s group will test whether thymulin can prevent metastatic tumors from forming and whether it can slow the growth of metastases that are already established. The experiments will use aged mice carrying breast cancer or melanoma, with complementary studies conducted on human cells in the laboratory.

The investigators are particularly interested in the possibility of using thymulin as an add-on treatment for older patients receiving immune checkpoint inhibitors. Drugs targeting PD-1 or PD-L1 can restore the activity of exhausted T cells, but only a portion of patients benefit. Chronic inflammation may contribute to treatment resistance by disrupting immune coordination and creating conditions that favor tumor survival. If thymulin can reduce this inflammatory interference without suppressing anti-tumor immunity, it could potentially improve responses to existing therapies. At this stage, however, the concept remains preclinical and has not been tested as a cancer treatment in patients.

Most cancer research has historically relied on young laboratory animals, even though cancer is primarily a disease of later life. Aging affects immune-cell production, metabolism, tissue structure and the chemical signals that regulate inflammation, meaning that results from young animals may not accurately predict how older patients respond. By conducting the new experiments in aged mice, the USC team hopes to model the biology of cancer and immunotherapy more realistically. “To treat diseases of aging, we need models that reflect the biology of aging,” Ito said. “Our goal is to make what we learn in the laboratory as relevant as possible to the patients most often affected by cancer.”

Subject of Research: Thymulin, age-related chronic inflammation, cancer progression, metastasis and immunotherapy response.

Web References: Keck School of Medicine of USC; USC news release on thymulin and age-related inflammation.

References: Nature Communications study by Fumito Ito and colleagues; National Institutes of Health grant 1R01CA316597-01.

Keywords: Thymulin, inflammaging, thymus, cancer immunotherapy, immunology, aging, chronic inflammation, metastasis, breast cancer, melanoma, PD-1, PD-L1, gerontology.

Spatial transcriptomics represents a transformative method in cancer biology, transcending traditional bulk sequencing by preserving spatial context and cellular heterogeneity. This advancement enables researchers to not only catalog which genes are active but to localize their expression within specific cell clusters and tissue regions, offering an unprecedented window into tumor microenvironments. The MD Anderson team capitalized on this technology to analyze 56 human lung tissue samples encompassing precursor lesions and advanced tumors from 25 patients. Validation with an independent cohort of 36 lesions from 19 patients ensured robustness, collectively comprising analysis of over 486,000 spatial transcriptomic spots and more than 5 million individual cells.

The study reveals that the earliest cancerous transformations occur in highly inflamed regions within lung tissue. These inflammatory hotspots are richly populated by proinflammatory cells, which surround alveolar cell populations that are predisposed to malignant progression. This proinflammatory milieu appears to act as a critical promoter of tumor initiation, setting the stage for subsequent genetic and epigenetic alterations. Such findings challenge the conventional focus solely on genetic mutations and highlight inflammation as a foundational biological process that may be harnessed for early intervention.

At the molecular level, the team’s analyses identified interleukin-1 beta (IL-1B) as a key inflammatory cytokine instrumental in this tumorigenic niche. Neutralization of IL-1B in experimental models significantly diminished the population of lung precursor cells, suggesting that IL-1B signaling underpins the early cellular changes that cascade into full-blown lung cancer. This discovery holds profound therapeutic implications, as targeted anti-inflammatory agents could intercept the disease at its inception, potentially reducing incidence and improving patient prognoses dramatically.

Notably, these spatial transcriptomic maps delineate a dynamic landscape where proinflammatory activity is not only spatially localized but temporally regulated, being most pronounced in early lung cancer phases and persisting in relevant murine models. The conservation of these inflammatory patterns across species bolsters the translational potential of the findings, providing a robust platform for developing inflammation-focused therapeutic strategies, either as monotherapies or in concert with existing treatments such as immunotherapy.

Immunotherapy, which has revolutionized the treatment of advanced lung cancer by mobilizing the immune system to attack tumor cells, may benefit from combination with inflammation-targeting agents. By reducing the proinflammatory environment that nurtures early tumor cells, such combination approaches could profoundly impede tumor initiation and progression, thereby expanding the arsenal of lung cancer interception tools.

This research underscores the importance of dissecting the tumor microenvironment with spatially resolved approaches that capture cellular interactions and functional states with exceptional granularity. Understanding the molecular drivers within these localized niches unveils hidden vulnerabilities and novel biomarkers for early detection and therapeutic targeting. The intricate mapping performed by the MD Anderson team paves the way for a new paradigm in oncology, where interception strategies are informed by spatial and temporal biology rather than static genomic snapshots.

Beyond therapeutic implications, the data generated by this study contribute to the broader field of functional genomics and tumor biology, enriching the scientific community’s understanding of neoplastic processes in the lung. The comprehensive dataset, encompassing millions of cells and hundreds of thousands of transcriptomic spots, offers a resource for future investigations into lung cancer initiation, progression, and resistance mechanisms.

The multidisciplinary collaboration that drove this work integrates expertise from translational molecular pathology, genomic medicine, and data science, exemplifying the power of convergent science. With support from prominent institutions and funding bodies—including the National Cancer Institute, CPRIT, and the James P. Allison Institute—the study stands as a testament to the transformative impact of investment in innovative cancer research technologies.

In summary, by illuminating the nexus between inflammation and the earliest lung cancer events through spatial transcriptomics, this study opens avenues for proactive cancer interception. Targeting inflammatory pathways, particularly IL-1B, represents a promising strategy to abrogate tumor initiation and enhance patient outcomes. As lung cancer remains a leading cause of cancer-related mortality worldwide, these insights hold significant promise for altering disease trajectories and herald a new era in precision oncology.

Subject of Research: Lung Cancer Initiation and Progression via Inflammation and Spatial Transcriptomics Mapping

Article Title: (Not explicitly provided; presumed from study: “Spatial Transcriptomic Profiling Reveals Inflammation-Driven Early Lung Cancer Initiation”)

News Publication Date: (Not specified in the source content)

Web References: https://faculty.mdanderson.org/profiles/humam_kadara.html, https://www.cell.com/cancer-cell/fulltext/S1535-6108(25)00445-3

References: Published in Cancer Cell; includes contributions from MD Anderson Cancer Center scientists, funded by several cancer research organizations

Image Credits: The University of Texas MD Anderson Cancer Center (Image of Humam Kadara, Ph.D.)

Keywords: Lung cancer, Inflammation, Immunotherapy, Tumorigenesis, Tumor development, Genomics, Functional genomics, Transcriptomics, Transcriptomes