Dendritic cells and immunity against cancer
From the Baylor Institute for Immunology Research and Sammons Cancer Center, Baylor University MedicalCenter, Dallas, TX; and Department of Gene and Cell Medicine and Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA
T cells can reject established tumours when adoptively transferred into patients, thereby demonstrating the power of the immune system for cancer therapy.
However, it has proven difﬁcult to maintain adoptively transferred T cells in the long term. Vaccines have the potential to induce tumour-speciﬁc effector and memory T cells.
However, clinical efﬁcacy of current vaccines is limited, possibly because tumours skew the immune system by means of myeloid-derived suppressor cells, inﬂammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells.
To improve the clinical efﬁcacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumour microenvironment.
This can be achieved by exploiting the fast increasing knowledge about the dendritic cell (DC) system, including the existence of distinct DC subsets that respond differentially to distinct activation signals, (functional plasticity), both contributing to the generation of unique adaptive immune responses.
We foresee that these novel cancer vaccines will be used as monotherapy in patients with resected disease and in combination with drugs targeting regulatory ⁄ suppressor pathways in patients with metastatic disease.
Gregory D. Pawelski