Cancer may not spread through the body in the same way during pregnancy, according to a study published in Nature Communications. Chen, Shi, Lei and colleagues report that pregnancy can create biological conditions that help tumor cells establish themselves in distant organs. Their work identifies a potential mechanism centered on adenosine, a signaling molecule that accumulates in tissues and influences immune activity. The findings suggest that pregnancy-associated changes in the immune system may unintentionally produce a more permissive environment for metastasis, the process responsible for most cancer-related deaths.
Metastasis is not simply a matter of cancer cells breaking away from a primary tumor and traveling through the bloodstream. Before tumor cells arrive, distant organs can undergo molecular and cellular changes that prepare what scientists call a pre-metastatic microenvironment, or pre-metastatic niche. This niche may alter blood vessels, connective tissue and immune-cell behavior, effectively making the destination more suitable for incoming cancer cells. The new study focuses on how pregnancy may influence this preparatory stage, particularly through changes in the activity of neutrophils.
Neutrophils are among the immune system’s most abundant and rapidly deployed cells. They are best known for attacking invading microbes, but they can also shape inflammation, tissue repair and tumor progression. In certain conditions, neutrophils become immunosuppressive, meaning that they reduce the ability of other immune cells to recognize or destroy abnormal cells. According to the study, pregnancy promotes the appearance or activity of such immunosuppressive neutrophils in tissues that may later serve as sites of tumor colonization.
The proposed trigger is adenosine, a naturally occurring molecule generated during cellular stress, inflammation and changes in tissue metabolism. Adenosine acts through specific receptors on the surface of immune cells, helping regulate the intensity of immune responses. In healthy circumstances, this pathway can prevent excessive inflammation and protect tissues from immune damage. In the context described by the researchers, however, increased adenosine signaling appears to reprogram neutrophils toward a state that suppresses antitumor immunity.
This distinction is important because pregnancy requires extensive immune adaptation. The maternal immune system must tolerate the developing fetus while continuing to protect the body from infection. Hormones, metabolites and tissue-derived signals all contribute to this carefully balanced state. The study suggests that adenosine-associated immune suppression, beneficial for maintaining pregnancy-related tolerance, may also weaken surveillance against disseminated cancer cells. In other words, a biological program designed to protect a developing fetus could create vulnerabilities that tumors exploit.
The research places particular emphasis on the pre-metastatic microenvironment rather than only on the primary tumor. This perspective helps explain why cancer progression can depend on organs and tissues that have not yet been invaded by malignant cells. If pregnancy-associated signals alter those sites in advance, they may influence whether circulating tumor cells survive after arrival, attach to local structures and begin forming secondary tumors. Immunosuppressive neutrophils could contribute by limiting the activity of cancer-fighting lymphocytes and by releasing factors that remodel surrounding tissue.
Adenosine is already attracting attention in cancer research because tumors can generate high levels of the molecule in oxygen-poor, metabolically stressed environments. Many experimental treatments aim to block adenosine receptors or the enzymes responsible for its production, with the goal of restoring immune activity. The findings from Chen and colleagues raise the possibility that similar pathways may operate beyond the tumor itself, including in distant organs affected by pregnancy. This could expand the search for therapeutic strategies targeting the earliest stages of metastatic preparation.
The study does not mean that pregnancy inevitably causes cancer to spread, nor does it suggest that pregnancy-associated immune changes are harmful in ordinary circumstances. Cancer behavior depends on tumor type, genetic features, treatment history, timing and many aspects of the host environment. The work instead identifies a mechanism that may help explain why pregnancy can influence metastatic risk in particular biological contexts. Further research will be needed to determine how broadly the mechanism applies across cancers and whether it can be detected or modified safely in patients.
The findings also highlight the complexity of designing cancer immunotherapies for people whose immune systems are undergoing major physiological changes. Blocking adenosine signaling could, in theory, enhance immune responses, but the pathway also contributes to tissue protection and immune balance. Any treatment would therefore need to distinguish harmful tumor-associated suppression from the normal regulation required during pregnancy. By connecting reproductive immunology with cancer biology, the study offers a framework for investigating how temporary physiological states can reshape the geography of metastasis.
As scientists continue to map the molecular events that precede metastatic disease, the new work presents pregnancy as more than a background condition. It may function as a powerful biological context capable of reorganizing immune cells and distant tissues. The central message is striking: before cancer cells arrive, the body may already be receiving signals that determine whether they can take hold. Adenosine-induced neutrophil suppression could be one of the molecular switches that helps establish that outcome, opening a new line of investigation into metastasis, immune regulation and pregnancy-associated cancer risk.
Subject of Research: Pregnancy-associated immune regulation and tumor metastasis
Article Title: Pregnancy promotes tumor metastasis through adenosine-induced immunosuppressive neutrophils in pre-metastatic microenvironment
Article References: Chen, C., Shi, J., Lei, Y. et al. “Pregnancy promotes tumor metastasis through adenosine-induced immunosuppressive neutrophils in pre-metastatic microenvironment.” Nature Communications (2026). https://doi.org/10.1038/s41467-026-76158-3
Image Credits: AI Generated
DOI: 10.1038/s41467-026-76158-3
Keywords: pregnancy, cancer metastasis, adenosine, neutrophils, immunosuppression, pre-metastatic microenvironment, tumor immunology, cancer biology
