Журнал клеточной науки и терапии

Журнал клеточной науки и терапии
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ISSN: 2157-7013


Necrosis-Associated Factors (DAMPs) Including S100A4 Used to Pulse Dendritic Cells (DCs) Induce Regulatory T cells

Ramin Lotfi, Denis Sebastian Wiegmann, Lisa Asseck, Alexander Erle, Tatjana Yildiz, Bernd Jahrsdörfer and Hubert Schrezenmeier

Emerging data support the immunosuppressive nature of the tumour microenvironment, which interferes with the efficacy of Dendritic Cells (DCs) used in cancer vaccination not only by rendering these immune cells unable to induce specific immune responses, but also by turning them into promoters of tumour growth.
A characteristic feature within the tumour microenvironment of advanced solid tumours is the necrotic cell death with subsequent release of necrosis-/Damage-Associated Molecular Patterns (DAMPs). DAMPs are known to induce tissue healing processes including angiogenesis and immune suppression, thus necrotic tumours harness the regenerative capacities of the host for their own survival and proliferation.
We examined the impact of DAMPs including S100A4 on DC-induced T cell proliferation. Human monocyte
derived DCs were pulsed with DAMPs obtained from necrotic tumour material or the specific DAMP-member S100A4. Pulsed DCs were subsequently co-cultured with autologous T cells. We could show enhanced metabolic activity and proliferation of CD4+CD25+FoxP3+regulatory T cells, which were capable of suppressing allogeneic lymphocytes in the mixed lymphocyte culture.
Given that necrotic material is generally found within advanced tumour tissue, there is an urgent need to
characterize specific members of DAMPs and their impact within the tumour microenvironment. By pointing out the crucial effect of S100A4 protein our results shed some light into the underlying mechanisms playing important roles in adaptive immune response to tumours. Given that S100 proteins are sensitive to oxidation it is conceivable that induction of oxidative microenvironmental conditions within the tumour tissue could abrogate necrosis induced immune suppression.