Rapid Autopsy to Define Dendritic Cell Spatial Distribution and T Cell Association in Lung Adenocarcinoma

Area of Science:

• Immunology
• Oncology
• Cancer Biology

Background:

• Immunotherapy efficacy correlates with conventional dendritic cell (cDC) presence.
• cDC type 1 (cDC1) drives CD8+ T cell activation, cDC type 2 (cDC2) influences CD4+ T cell responses, and regulatory cDCs can suppress anti-tumor immunity.
• Limited knowledge exists on human cDC distribution within the tumor microenvironment (TME), their prevalence in metastatic sites, and stage-dependent variations.

Purpose of the Study:

• To investigate the spatial distribution and prevalence of cDCs and other immune cells within the human lung adenocarcinoma TME.
• To compare cDC populations across different metastatic sites (lung, lymph node, liver).
• To analyze differences in cDC and immune cell proportions between early- and late-stage lung adenocarcinoma.

Main Methods:

• Utilized rapid autopsy specimens from 10 lung adenocarcinoma patients.
• Employed multiplex immunofluorescence with 18 markers to analyze 42 tumors.
• Quantified T cells, cDC1, cDC2, mature regulatory DCs, and macrophages.

Main Results:

• T cells, cDC1, and cDC2 were primarily located in the stroma, while mature regulatory DCs were enriched within the tumor.
• Lung and lymph node tumors showed higher enrichment of T cells and cDCs compared to liver tumors.
• Late-stage disease exhibited increased proportions of cDC2 and macrophages, unlike T cells and cDC1 which remained consistent across stages.

Conclusions:

• cDC subsets display distinct localization patterns within the lung adenocarcinoma TME, suggesting specialized functions.
• Metastatic site influences the immune cell composition, with liver metastases showing less immune infiltration.
• Stage-dependent alterations in cDC2 and macrophage populations indicate evolving immune regulation in advanced lung adenocarcinoma, with potential therapeutic implications.