Allogeneic Dendritic Cells in Cancer Immunotherapy: A Clinical and Experimental Perspective

Cancer Immunotherapy

Cancer immunotherapy is facing times of tremendous recognition and has become a clinically validated option for many cancers .The major immunotherapeutic breakthrough in efforts to eradicate malignancies came with the development of immune checkpoint inhibitors which re-energize cancerspecific T-cells . Although effective against certain malignancies the majority of cancer patients do not benefit from checkpoint inhibitors . To work, they require the pre-existence of cytotoxic CD8+ T cells recognizing Tumor-Associated Antigens [TAA]. It is evident that some form of cancer vaccine is needed to induce such TAA-directed T cells in cancer patients where checkpoint inhibitors are not yet working. Dendritic cell [DC]- based immunotherapy is a strategy to provoke T-cell-mediated anti-tumor immunity by taking advantage of the antigenpresenting capacities of these cells. Autologous DCs can be manipulated to present Tumor-Associated Antigens [TAAs] when injected into cancer patients, in order to prime naive cytotoxic CD8+ T cells against malignant cells.

Initially efforts to vaccinate with DCs were based on the direct presentation capacity of such cells, which were expected to migrate to lymph nodes and prime CD8+ T cells. However, this type of vaccination has low objective tumor-response rates . Accumulating evidence argue that it is the bystander host DCs, instead of the injected TAA-loaded DC, mediating the priming of CD8+ T cells . In the paper by Liu et al. autologous DCs, by acting as immune enhancers, orchestrate the recruitment and activation of bystander DCs and Natural Killer [NK] cells through the secretion of pro-inflammatory factors, in order to prime CD8+ T cells. This capacity of DCs to secrete immune cell recruiting factors has also been observed during viral infections, where infected cells can cross-talk and activate non-infected bystander DCs in order to prime functional T-cell responses . Notably, the secretion of pro-inflammatory signals as a third signal during priming of tumor-specific T cells is among the key criteria imposed by a consensus for the production of successful cancer-vaccines . Though initially it was expected that these secretory capacities were related only to direct T-cell polarization and activation, stimulation of other immune cells including bystander DCs can occur.

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Sarah Jhonson
Managing Editor
International Journal of Case Reports
Email: caserep@emedicalsci.org