"..despite no major changes in our treatment system, the prognosis began to deteriorate from 2021 and worsened significantly after 2022. This period coincided exactly with the start of vaccination.."
Pancreatic Cancer Prognosis Worsened After Repeated Covid-19 Vaccination
Makoto Abue, MD
Department of Gastroenterology
Miyagi Cancer Center Nodayama 47-1, Medeshima-Shiote, Natori
Miyagi, Japan, 981-1293 (7/2025)
+81-22-384-3151 tel / +81-22-381-1174 (FAX)
abue-ma742@miyagi-pho.jp
“Repeated COVID-19 Vaccination as a Poor Prognostic Factor in Pancreatic Cancer: A Retrospective, Single-Center Cohort Study. Cancers (Basel). 2025 Jun 16;17(12):2006. PDF (Author Updated 7-10-25)
Kirk Hamilton: Can you please share with me your educational background and current position?
Makoto Abue: First, let me introduce myself. After graduating from Jichi Medical University in 2000, I worked in community medicine for seven years following two years of initial training. Since then, I have worked at the Miyagi Cancer Center for approximately 16 years. During this time, I conducted research on microRNA (miRNA) and obtained a Ph.D... I specialize in gastroenterology and oversee the biliary tract and pancreatic areas. I am currently the head of the gastroenterology department. The academic societies I belong to include the Japanese Society of Gastroenterology, Japan Gastroenterological Endoscopy Society, Japan Pancreas Society, and Japan Biliary Association. I mainly perform endoscopic examinations and treatments of the biliary tract and pancreas, as well as chemotherapy. My lifelong goal is to improve pancreatic cancer prognosis. To that end, I am interested in finding tests and treatments that lead to better prognoses. Conversely, I am interested in avoiding or overcoming those that may lead to poor prognoses. My intention is to provide pancreatic cancer patients with as many benefits as possible.
KH: What got you interested in studying the role of repeated Covid vaccinations and pancreatic cancer prognosis?
MA: As shown in our paper, the prognosis of pancreatic cancer gradually improved until 2020 due to the developments in diagnosis and treatment. However, despite no major changes in our treatment system, the prognoses began to deteriorate from 2021 and worsened significantly after 2022. This period coincided exactly with the start of Covid vaccination, raising concerns that the booster vaccination was having a negative impact. Under these circumstances, I further questioned the situation where repeated vaccinations of three, four, five or six times in a short period of time were recommended. In Japan, there is a lack of sufficient verification of actual clinical data (real-world data) on the efficacy and safety of repeated vaccinations, including additional vaccinations. In particular, we believe that more research is needed on evidence related to additional vaccinations. We have been waiting for the government to conduct such verification, but, as there has been no progress, we have decided to investigate the effects of additional vaccinations at our facility.
KH: What is the significance of IgG4 levels in cancer and pancreatic cancer patients specifically? What does the term “immune suppressor” with regards to IgG4 levels mean?
MA: IgG4, one of the subclasses of IgG, has attracted attention due to its role in allergic reactions and autoimmune diseases. IgG4-related diseases are a group of diseases characterized by the infiltration of organs with IgG4-positive plasma cells and lymphocytes, accompanied by fibrosis. In the field of pancreatic diseases, these diseases are of interest due to the need to differentiate them from cancer through imaging, as well as their association with cancer. In healthy individuals, IgG4 accounts for only a few percent of all IgGs. The Fc region of IgG4 is characterized by its inability to activate complement C1q and its low binding affinity for Fcγ receptors. This property of IgG4 suppresses excessive Fcγ receptor-mediated immune responses. Furthermore, IgG4 is thought to exert anti-inflammatory effects by becoming a functional unit through Fab arm exchange. Production of IgG4 is induced by antigen stimulation and Th2-type cytokines, such as IL-4 and IL-13. It has also been reported that activation of IL-10-producing regulatory T cells in a Th2-dominant environment further promotes IgG4 production. Thus, high levels of IgG4 suggest that the organism may be shifting toward immunosuppression and anti-inflammation.
KH: When you say “spike-specific” IgG4 levels I am assuming you are referring to the spike protein? Why only measure “spike-specific” IgG4 levels? Why not also measure the nucleocapsid IgG4 levels to the SARSCov2 virus?
MA: In our paper, “spike-specific” means “spike protein-specific”. This study did not consider nucleocapsid proteins. These proteins are important for studying antibody dynamics, including the effects of infection, and they may further clarify the relationship between vaccines and the immune response. In this study, we examined the prognosis of pancreatic cancer patients who received repeated vaccinations. Our focus was on the impact of repeated vaccination rather than infection. Previous studies have reported that repeated mRNA vaccination increases spike protein-specific IgG4. The aim of this study was to validate this finding and determine whether there is a relationship between IgG4 and the poor prognosis of pancreatic cancer. Based on these results, spike-specific IgG4 alone was sufficient for evaluation, and nucleocapsid protein was not measured. However, nucleocapsid proteins may provide additional insight, and this study is a topic for future investigation.
KH: Is the spike protein the “toxic,” “inflammatory” or “procarcinogenic” component of the Covid vaccination/booster?
MA: The mRNA-LNP platform produces spike proteins and stimulates the production of antibodies. Our study showed that individuals who received three or more doses of the mRNA vaccine had elevated IgG4 levels. The shift to IgG4 is notable for its immunosuppressive and anti-inflammatory properties, and it is an active area of research. Some hypothesize that this response may be due to, or contribute to, excessive or prolonged immune activation. Conversely, others suggest that it is a mechanism of immune tolerance to repeated exposure to the antigen. The precise clinical significance of IgG4 elevation after multiple vaccinations and the role of spike proteins in the potential inflammatory process are topics for future research. Mentioning the "toxicity" and "carcinogenicity" of spike proteins in this study may be difficult. Nevertheless, concerns have been reported about the organ-damaging properties of the spike protein, including its effects on the heart, blood vessels, nerves, and ovaries. Regarding carcinogenicity, some experts are concerned about SV40 contamination, estrogen receptor effects, and effects on tumor suppressor genes. We believe these concerns require further validation.
KH: Can you tell us a little bit about your study and the basic results?
MA: In our study, when we investigated prognosis in overall survival of pancreatic cancer, we found that those who received 3 or more COVID-19 vaccinations had significantly shorter survival. And when we investigated IgG4 among them, we found that IgG4 was elevated in patients who had received three or more vaccinations, again indicating a poor prognosis (IgG4 was particularly elevated in patients with short prognoses, such as those who died within 90 days). Additionally, regulatory T cells were also prominent in cancer cells of frequent vaccinators and those with high IgG4 levels. It was suggested that frequent vaccinations may lead to immune evasion of cancer, creating an environment conducive to cancer growth. We further investigated the relationship between spike-specific IgG4 and total IgG4. The results showed that spike-specific IgG4 increased markedly with increasing vaccination frequency. Spike-specific IgG4 was positively correlated with total IgG4, and those with elevated spike-specific IgG4 also tended to have higher total IgG4 levels. In other words, repeated mRNA vaccination over a short period of time tended to elevate IgG4, suggesting that the immune balance may have shifted toward suppression. However, this is a single-center, retrospective cohort study with a limited number of cases. Therefore, we believe that further large-scale validation and discussion are needed. We hope that our paper will serve as a starting point.
KH: In your opinion should Covid boosters not be recommended in pancreatic cancer patients? How about cancer patients in general? Should they get Covid vaccinations, boosters or initial injections?
MA: Based on the results of this study, I would personally be reluctant to recommend short-term, repeated vaccination for all solid tumors, including pancreatic cancer. Our findings may be applicable to many cancer patients. However, our results are based on a single hypothesis from a single-center, retrospective cohort study and are open to further discussion. Public health agencies continue to make recommendations for cancer patients, and we refer readers to these agencies for comprehensive reviews. To date, the benefits have been considered to outweigh the risks. Nevertheless, breakthrough infections following vaccination are now common, and the virus has been attenuated. The number of peer-reviewed papers on various adverse effects is also increasing. For better public health policy, we believe that the efficacy and safety of vaccines need to be reexamined and debated.
KH: There has been a term called “turbo cancers” in public social media circles associated with the Covid vaccines. Meaning more cancers occurring in younger patients, with faster progression, or quicker recurrence of cancers and more rapid progression to death in patients with prior cancers. Might this above observation, the elevated IgG4 spike specific antibody levels in cancer patients with more rapid progression, be a cause of these “turbo cancers” and a sound reason not to get further Covid immunizations?
MA: Due to the risk of myocarditis and the low severity of the infection, caution should be exercised when considering the vaccination of young patients. Furthermore, the results of this study suggest that repeated vaccination in a short period of time may not benefit cancer patients. Whether these results are sufficient reason to avoid vaccination requires extensive validation and debate among public health authorities, academics, and the general public.
KH: Are you aware of any way to lower the “spike-specific IgG4” levels? i.e Nattokinase, bromelain, curcumin, NAC, etc.) 1) 2) 3) 4) (See Base Spike Protein Detoxification algorithm halfway down the page)
MA: I don't know of any way to reliably lower it. However, the half-life of IgG4 is usually about three weeks. I believe that it will settle down if there are no repeated vaccinations or infections within a short period of time. Once chronic antigenic stimulation ends and the body clears spiked proteins, I believe the immune balance will gradually normalize. There may be individual differences, depending on one's ability to process the spike protein. Of course, using the method described in the link may be a good idea.
KH: Do you ever measure quantitative IgG spike protein antibodies in those cancer patients who have been vaccinated and see if higher levels of these spike protein antibodies is correlated to recurrence?
MA: Our institution has not studied the quantification of spike-specific IgG antibodies and cancer recurrence. Due to our current clinical workload and limited research and human resources, it is difficult to continue and develop research independently at our institution. (However, if the idea of a collaborative study with another facility emerges, we may consider the study).
KH: Any closing thoughts you may have on this very interesting and timely topic?
MA: Thank you for this interview today. I appreciate your interest in my research. I hope it will give as many people as possible an opportunity to think about vaccination and their own immunity.
KH: Thank you Dr. Abue for your timely, detailed, credible and critically important work which may save lives and much human suffering.
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