“The carcinogenic risk associated with these technologies, which has long been known within the gene therapy field, represents an area of research that cannot be ignored, given the fundamental principle of medicine “primum non nocere” (first, do no harm).”
The rapid development and global deployment of mRNA vaccines for COVID-19 represented a landmark achievement in public health. However, the novel mechanism of these “genetic vaccines”—technically pro-drug gene therapies encased in lipid nanoparticles—has prompted ongoing scientific inquiry into their potential long-term effects.
A comprehensive case report and review, titled “Exploring the potential link between mRNA COVID-19 vaccinations and cancer: A case report with a review of haematopoietic malignancies with insights into pathogenic mechanisms” published in Oncotarget by an international team of researchers investigates a consequential scientific question: whether there could be a link between mRNA COVID-19 vaccines and the development of haematopoietic cancers.
Led by first author Patrizia Gentilini, along with corresponding author Panagis Polykretis of the “Allineare Sanità e Salute” Foundation and Independent Medical Scientific Commission (CMSi), Milano, the paper presents a detailed case study alongside a systematic review of existing literature. It does not claim to have proven a causal link, but instead argues that the convergence of clinical observations and proposed biological mechanisms warrants deeper, more urgent investigation.
The Case Report
The report centers on a 38-year-old, healthy, athletic woman with no significant family or medical history. Routine blood work in April 2021 showed only mild leukopenia (white blood cells at 2,450/μL), which her physician did not prioritize.
She received her first dose of the Pfizer/BioNTech (Comirnaty®) vaccine on June 20, 2021, with no immediate issues. However, the morning after her second dose on July 19, 2021, she experienced severe symptoms: fever, locked neck and jaw, tinnitus, nausea, diffuse pain, headache, and sweating. These symptoms worsened over subsequent days, accompanied by insomnia and hypersensitivity to temperature changes and noise.
Over the following months, laboratory testing revealed a pattern of progressive deterioration: persistent neutropenia, rising lymphocytosis, and a steadily climbing erythrocyte sedimentation rate (ESR) from 59 mm/hour in August to 118 mm/hour by October. A rheumatologic examination in late October suggested post-vaccination polymyalgia rheumatica. A PET scan on November 15, 2021, revealed intense uptake in the bone marrow of the entire axial and appendicular skeleton, as well as the spleen. Bone marrow biopsy on December 1, 2021, delivered the diagnosis: B-lymphoblastic leukemia/lymphoma, with approximately 95% of nucleated cells replaced by blast-like elements. The patient underwent chemotherapy and achieved remission, though she later suffered a central nervous system relapse in early 2025.
Broader Patterns: A Review of the Literature
To contextualize this single case, the authors conducted a systematic review of the medical literature from December 2020 to October 2025. They identified 30 studies documenting new-onset or rapidly recurring malignancies shortly after mRNA COVID-19 vaccination. The overwhelming majority (28 of 30) were hematolymphoproliferative disorders—cancers of the blood and lymph system.
Among the case reports, they found 9 cases of B-cell lymphoproliferative disorders, 13 involving the T-cell lineage, 6 affecting the myeloid line, and 2 cases of solid tumors. The Pfizer/BioNTech vaccine appeared most frequently (16 cases). The onset of symptoms following vaccination was often remarkably brief, in some cases occurring within days. Several lymphomas arose at the injection site itself, while others manifested in vaccine-draining lymph nodes such as the axillary and cervical regions.
One particularly instructive case involved angioimmunoblastic T-cell lymphoma, where rapid progression was observed immediately after a booster dose. A PET scan just eight days after boosting showed a dramatic increase in hypermetabolic lesions, with notably asymmetrical progression on the side of the booster injection.
Proposed Pathogenic Mechanisms
The paper’s core contribution is its detailed exploration of potential biological mechanisms by which mRNA vaccines could theoretically promote oncogenesis. These mechanisms are drawn from in-vitro, pre-clinical, and related scientific literature, and the authors emphasize that specific studies in humans remain lacking.
The first proposed mechanism involves the alteration of the PD-1/PD-L1 immune checkpoint. Studies have shown increased expression of programmed death-ligand 1 (PD-L1) on peripheral blood granulocytes and monocytes in vaccinated individuals. PD-L1 acts as an “off switch” for T-cells, suppressing their activity and potentially impairing the immune system’s ability to surveil and eliminate emerging cancer cells. This immune checkpoint alteration could create a permissive environment for malignant transformation.
A second mechanism suggests an interaction between the spike protein and tumor suppressors. The S2 subunit of the spike protein has been shown in silico to interact with critical tumor suppressor proteins including p53, BRCA1, and BRCA2. These proteins normally regulate cellular responses to stress and prevent cancer development. Interference with their function, as demonstrated in cancer cell lines where spike protein expression suppressed p53 activation, could disable fundamental safeguards against uncontrolled cell proliferation.
A third concerns the impairment of Type I interferon signaling. Type I interferons play essential roles in inflammation, immunomodulation, and tumor cell recognition. Differential gene expression analysis has revealed that while COVID-19 patients show dramatic upregulation of type I and type II interferons, vaccinated individuals do not. This suggests that the genetic vaccines may actively suppress type I interferon production, potentially blunting a key anti-tumor immune defense. Interferons normally induce cell cycle arrest, promote apoptosis, and activate natural killer cells and CD8+ T-cells—all critical for cancer surveillance.
The authors also explore additional mechanisms, including increased transforming growth factor beta production promoting epithelial-mesenchymal transition, DNA contamination with SV40 promoter elements posing insertional mutagenesis risk, reverse transcription of vaccine mRNA via LINE-1 elements, IgG4 class switching leading to immune evasion, and ribosomal frameshifting producing off-target proteins with unknown effects.
Future Perspectives and Conclusion
The proposed link between mRNA COVID-19 vaccines and cancer does not claim to provide a complete explanation of post-vaccination malignancies. Rather, it offers a structured framework for understanding how multiple mechanisms may combine to produce oncogenic outcomes in susceptible individuals. By integrating clinical observations, laboratory findings, and mechanistic insights from molecular biology, the review clarifies how vaccine components and host factors may interact.
The authors emphasize that the carcinogenic risk associated with gene therapy technologies has long been recognized and cannot be ignored in the context of genetic vaccines administered to healthy populations. They call for extensive pharmacodynamic, pharmacokinetic, and genotoxicity evaluations, as well as population-based observational studies comparing cancer incidence in vaccinated versus unvaccinated populations. Such research, they argue, is essential to assess potential carcinogenic risk and understand pathogenic mechanisms, reminding readers of the fundamental principle of medicine: primum non nocere—first, do no harm.
Click here to read the full case report published in Oncotarget.
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