Tissue-specific properties of type 1 dendritic cells in lung cancer: implications for immunotherapy
Lucía Ines Lopez Rodriguez1, Roberto Amadio1,2, Giulia Maria Piperno1
1Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
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.
Insights
Type 1 conventional dendritic cells (cDC1s) are crucial for anti-tumor immunity in non-small cell lung cancer (NSCLC). Harnessing lung cDC1s may improve checkpoint inhibitor therapy effectiveness.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Checkpoint inhibitors improve non-small cell lung cancer (NSCLC) treatment but have limited response rates.
- Tumor-infiltrating immune cells, particularly T cells and myeloid cells, play a key role in anti-tumor responses.
- Type 1 conventional dendritic cells (cDC1s) are vital for initiating anti-tumor T cell immunity.
Purpose of the Study:
- To review recent findings on the induction and regulation of anti-tumor T cell responses in NSCLC.
- To focus on the specific role of lung-resident cDC1s in orchestrating anti-tumor immunity.
- To highlight strategies for enhancing cDC1 function to improve NSCLC immunotherapy.
Main Methods:
- High-dimensional analysis of clinical NSCLC samples.
- Mechanistic experiments using NSCLC models.
- Dissection of functional states and spatial distribution of lung cDC1s.
- Analysis of cDC1 impact on T cell responses to neoantigens.
Main Results:
- Lung-resident cDC1s are abundant, long-lived, and possess a unique tissue-specific gene program.
- cDC1s effectively induce effector CD8 T cells against neoantigens.
- The functional states and spatial distribution of lung cDC1s vary across tumor stages.
- cDC1s significantly impact T cell responses to neoantigens in the lung tumor microenvironment.
Conclusions:
- Lung cDC1s are central players in lung cancer immunity, distinct from cDC1s in other tissues.
- Understanding lung cDC1 biology is critical for improving NSCLC immunotherapy.
- Emerging strategies aim to leverage lung cDC1s to enhance anti-tumor T cell responses and patient outcomes.
