Pro-tumor Tfh2 cells induce detrimental IgG4 production and PGE2-dependent IgE inhibition in pancreatic cancer

De Monte, Lucia; Clemente, Francesca; Ruggiero, Eliana; Pini, Raffaella; Ceraolo, Maria Grazia; Schiavo Lena, Marco; Balestrieri, Chiara; Lazarevic, Dejan; Belfiori, Giulio; Crippa, Stefano; Balzano, Gianpaolo; Falconi, Massimo; Doglioni, Claudio; Bonini, Chiara; Reni, Michele; Protti, Maria Pia

doi:10.1016/j.ebiom.2023.104819

Cited by 2 publications

(1 citation statement)

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“…Immune modulation towards the type 2 helper T (Th2) cells immunity bias was reported in glioblastoma patients as measured by increased serum levels of IgG4, M2 monocyte cells, IL-4, IL-10, and IL-13 [39]. Finally, high levels of serum IgG4 have also been reported in cholangiocarcinoma [40] and pancreatic cancer [41][42][43], while higher tissue IgG4 levels have been reported in papillary thyroid carcinoma [44], extrahepatic cholangiocarcinoma [45], and pancreatic cancer [46]. Most crucially, however, it is the "hyperprogressive disease" phenomenon that has been associated with some cancer treatments involving IgG4 antibodies such as nivolumab, which uses IgG4 with a stabilizing S228P mutation [35].…”

Section: Igg4s In Cancer Developmentmentioning

confidence: 99%

Exploring the possible link between the spike protein immunoglobulin G4 antibodies and cancer progression

Raszek,

Cowley,

Redwan

et al. 2024

Explor Immunol

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Repeated inoculation with messenger RNA (mRNA) vaccines elicits immunoglobulin G4 (IgG4) antibody production. Such an increase in the concentration of specific and non-specific IgG4 antibodies allows the growth of some types of cancer by blocking the activation of effector immune cells. This work proposes the hypothesis that cancer growth may be indirectly promoted by increased concentrations of non-specific IgG4 antibodies by the following mechanisms: 1) IgG4 antibodies can bind to anti-tumor IgG1 antibodies and block their interaction with receptors located on effector cells, thus preventing the destruction of cancer cells, 2) IgG4 can interact with fragment crystallizable gamma receptor IIb (FcγRIIB) inhibitory receptors, thus reducing effector functions of innate immune cells, and 3) targeting of specific epitopes by IgG4 could be oncogenic by inducing the production of a microenvironment that can promote cancer development. This article reviews the supporting literature and suggests several experimental protocols to evaluate this hypothesis in the context of repeated inoculation with mRNA vaccines. Additionally, this work proposes some management options aimed at reducing the unfavorable molecular consequences that could mediate cancer development when encountering high concentrations of IgG4 antibodies.

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