"Since nucleoside-modified mRNA vaccines strongly activate T follicular helper cells, it is important to explore the possible impact of approved SARS-CoV-2 mRNA vaccines on neoplasms affecting this cell type. Herein, we report and discuss unexpected rapid progression of lymphomatous lesions after administration of a BNT162b2 mRNA vaccine booster in a man recently diagnosed with AITL [AngioImmunoblastic T cell Lymphoma].
Introduction
The remarkable efficiency of nucleoside-modified SARS-CoV-2 mRNA vaccines has been related to their ability to induce a potent stimulation of T follicular helper (TFH) cells, resulting in persistent germinal center B cell responses. Clinically, this might translate into reactive lymphoadenopathy which sometimes may raise a differential diagnosis with a lymphoproliferative disorder. At the same time, the possible impact of SARS-CoV-2 mRNA vaccination on pre-existing peripheral T cell lymphoma is still to be determined...
Discussion
... To the best of our knowledge, this is the first observation suggesting that administration of a SARS-CoV-2 vaccine might induce AITL progression. Several arguments support this possibility. First, the dramatic speed and magnitude of the progression manifested on two 18F-FDG PET-CT performed 22 days apart. Such a rapid evolution would be highly unexpected in the natural course in the disease. Since mRNA vaccination is known to induce enlargement and hypermetabolic activity of draining lymph nodes, it is reasonable to postulate that it was the trigger of the changes observed. Indeed, the increase in size and metabolic activity was higher in axillary lymph nodes draining the site of vaccine injection as compared to their contralateral counterparts. However, pre-existing lymphomatous nodes were also clearly enhanced as compared to the first test. Moreover, new hypermetabolic lesions most likely of lymphomatous nature clearly appeared at distance of the injection site.
In fact, the supposed enhancing action of the vaccine on AITL neoplastic cells is fully consistent with previous observations identifying TFH cells within germinal centers as key targets of nucleoside-modified mRNA vaccines both in animals and in man. Malignant TFH cells, the hallmark of AITH, might be especially sensitive to mRNA vaccines when they harbor the RHOA G17V mutation which was present in our case. Indeed, this mutation facilitates proliferation and activation of several signaling pathways in TFH cells. Furthermore, mice genetically engineered to reproduce the RHOA G17V and TET2 mutations—both were present in our case—develop lymphoma upon immunization with sheep red blood cells. This experimental observation is relevant to RNA vaccines as RNA of sheep red blood cells was shown to be responsible for their ability to stimulate TFH and induce germinal center reaction...
Conclusion
This observation... suggests that vaccination with the BNT162b2 mRNA vaccine might induce rapid progression of AITL."
Copyright © 2021 Goldman, Bron, Tousseyn, Vierasu, Dewispelaere, Heimann, Cogan and Goldman.
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