Myeloid networks and the lymph node microenvironment during tumor development
Advances in immunotherapy have meant that patients with previously refractory tumors are now treatable; unfortunately, these therapies are only effective in a small subset of patients. This lack of efficacy has mainly been ascribed to the fact that the tumor has multiple local mechanisms of immune suppression. Whilst these sources of local immunosuppression are important, systemic changes occurring during tumor development have wide ranging impacts on the host and have the potential to exert broader effects on the development of anti-tumor immune responses. In fact recent work has shown that therapeutic vaccination against tumor antigens can synergise with immunotherapy suggesting that improving priming against tumor antigens is likely to be critical in improving outcomes of immunotherapy. We recently identified that dendritic cells expressing CD103 are the critical population for priming the CD8+ T cell response in the draining lymph node during tumor development in mice. Clinical data suggests a similar role for the human equivalent of these cells, the CD141+ dendritic cell. We are continuing to dissect the myeloid network within the lymph node and to look for defects in both cellular phenotype and spatiotemporal localization during tumor development.
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