Figure 3. The mechanisms of enhanced Th17 cellular differentiation in
cancer(+) patients after mRNA vaccination, facilitated by the SARS-CoV-2
spike protein. The induction of IL-6 and TNF-α, via the NF-κB response
to spike, and the TGF-β induced expression of RORγt, enhances the
generation of a Th17 population of cells that is responsible for the
development of autoimmunity [166-169,172,173].
On top of this, the spike protein potentiates the signalling of the
epidermal growth factor receptor (EGFR) [177]. Persistent activation
of STAT3 is a common feature of the tumor microenvironment and a major
contributor to the inflammatory state [178]. An intense activation
of STAT3 can result from 1) an aberrant expression of IL-6 and
subsequent stimulation of the IL-6 receptor [179], and 2) an intense
activation of EGFR signalling as imposed by the spike protein [177].
These molecular events, illustrated in Figure 4, when they are happening
concurrently, have the potential to bypass the inhibitory checkpoint of
negative regulator suppressor of cytokine signalling 3 (SOCS3). SOCS3
would otherwise deactivate JAK in order to diminish STAT3 activation
[179]. Moreover, the abnormally elevated expression of IL-6 and
JAK/STAT3 signalling are pro-tumorigenic and enhance the differentiation
of Th17 cells [179,180].