Tissue-specific properties of type 1 dendritic cells in lung cancer: implications for immunotherapy.

Abstract

Checkpoint inhibitors have led to remarkable benefits in non-small cell lung cancer (NSCLC), yet response rates remain below expectations. High-dimensional analysis and mechanistic experiments in clinical samples and relevant NSCLC models uncovered the immune composition of lung cancer tissues, providing invaluable insights into the functional properties of tumor-infiltrating T cells and myeloid cells. Among myeloid cells, type 1 conventional dendritic cells (cDC1s) stand out for their unique ability to induce effector CD8 T cells against neoantigens and coordinate antitumoral immunity. Notably, lung resident cDC1 are particularly abundant and long-lived and express a unique tissue-specific gene program, underscoring their central role in lung immunity. Here, we discuss recent insights on the induction and regulation of antitumoral T cell responses in lung cancer, separating it from the tissue-agnostic knowledge generated from heterogeneous tumor models. We focus on the most recent studies dissecting functional states and spatial distribution of lung cDC1 across tumor stages and their impact on T cell responses to neoantigens. Finally, we highlight relevant gaps and emerging strategies to harness lung cDC1 immunostimulatory potential.