Abstract
Total tumor RNA pulsed dendritic cells plus adoptive transfer of ex-vivo enriched autologous T-lymphocytes in the treatment of children with primary brain tumors
Highlights
Primary pediatric central nervous system tumorsPediatric brain tumors are the commonest solid tumors in children and the cause for the most cancer related mortality in this age group[1]
The mechanisms by which lymphodepletion leads to an enhancement of immune responses in humans are not well elucidated but elegant murine studies have implicated the following important processes: (1) increased in production of homeostatic cytokines such as IL-7 and IL-15 that drive lymphocyte proliferation[93]; (2) decreased competition with adoptively transferred tumor-specific lymphocytes through removal of “cytokine sinks” consisting of host lymphocytes and natural killer (NK) cells that decrease the bioavailability of growth factors[94]; (3) removal of CD4+CD25+Fox P3+ tregs that attenuate anti-tumor immunity[95]; (4) increased toll-like receptor agonistic signals and inflammatory cytokines through release of gut microbial antigens such as endotoxin during damage to gut endothelium by MA therapy[96]; and (5) direct enhancing effects of hematopoietic stem cell (HSC) transplant on the in vivo expansion and function of adoptively transferred lymphocytes[97]
It is obvious that success in a larger proportion of treated children is unlikely to equal what has been observed in adults with metastatic melanomas
Summary
Primary pediatric central nervous system tumorsPediatric brain tumors are the commonest solid tumors in children and the cause for the most cancer related mortality in this age group[1].
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