STAT-3 signaling from the tumors blocks the pro-inflammatory cytokines, so no danger signal is sent to the immune system.
The Missing Link in T-cell activation using a Vaccine, "The Danger Signal"
DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.
Tumor bed is heavily infiltrated by DCs, which, as shown here, are the most efficient inducers of human Th17 cells. The data supports a model in which Th17 cells are recruited to the tumor bed by Th17-attracting chemokines (eg, CCL20, recently shown to be enriched in the melanoma tumor bed) and activated to a Th17 phenotype locally by tumor-infiltrating DCs. The capacity of DCs to induce Th17 cells may be further enhanced by the uptake of apoptotic tumor cells, as well as inflammatory cytokines (eg, IL1, IL6, TNF) in the tumor bed. This gives rise to T-cell activation and the inflamed response leading to immune response.
For the tumor to survive the immunologic suppression system, it must turn on pathways (such as Stat3) that inhibit production or sensing of proinflammatory danger signals that activate innate and adaptive immune responses. Tumors that successfully accomplish this can shift the balance of immunity from activation to tolerance induction. Pardol et al But what if, the production of Proinflammatory cytokines can over come the suppressive function of the tumor’s microenvironment? Could the differentiation of the CD4+ T-cells into Th17 be the path to activation and immunity responses? If that is the case, then Anti-CTLA-4 blockade (ipilimumab) plays more of a major factor in adaptive immunity then we originally thought.
“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B
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