Immunotherapy exploits the patients’ own immune system to attack its cancer cells. Despite recent successes however, lung cancer remains the leading cause of cancer-related death. Recent clinical observations link the immunological state of the lung tumor microenvironment (TME) to patient prognosis and response to immunotherapy. Therefore there is an unmet need to explore the decisive ‘X factors’ within the lung TME that can tip the balance towards effective antitumor immunity.
A TME-residing subset that already gained attention in several other cancer types is the type 1 dendritic cell (cDC1) due to its unparalleled capacity to induce antitumor immunity. Since its role within the lung TME has not been elucidated so far, we are determined to explore their decisive character in lung tumor progression in this project. In order to explore the lung TME residing cDC1 specifically we propose to develop an innovative targeting strategy, termed the ‘Nanofactory’. This is based on cDC1-specific nanobodies fused to a gene-of-interest (GOI) produced by the lung cancer cells themselves. The GOIs in this project are fluorescent to visualize cDC1-specific targeting, or cDC1-stimulating to explore the boosting effect of the lung TME-residing cDC1.
In sum we want to develop an approach to explore the cDC1 population residing in lung tumors from within and as such define the 'X factor' of lung tumor immunotherapy.