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Author Spotlight: Unlocking Insights into the Immune Cell Landscape of Tumors
Published on: August 18, 2023
Immune cell landscape in therapy-naïve squamous cell and adenocarcinomas of the lung
Luka Brcic1, Stefanie Stanzer2, Dagmar Krenbek3
1Institute of Pathology, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010, Graz, Austria. luka.brcic@medunigraz.at.
Abstract:
Squamous cell and adenocarcinomas of the lung develop different mechanisms during carcinogenesis to evade attacks of the immune system. Besides the well-known check-point control programmed death 1 and its ligand, many more mechanisms, acting either tumoricidal or in favor of tumor progression, exist. Analysis of the immune cell profiles in resected tissues and bronchoalveolar lavage samples and correlation between them and with overall survival data was performed. In all tumor samples in this study, cells of the immune system expressed a tumor-cooperating phenotype. High numbers of regulatory T cells, or alternatively expression of Vista on lymphocytes was present. Tumoricidal dendritic cells were absent in tumor tissue, and barely present in bronchoalveolar lavage, whereas tumor-friendly monocytoid and plasmocytoid dendritic cells were seen in both. Alveolar macrophages were predominantly differentiated into tumor-cooperating M2 types, whereas tumoricidal M1 macrophages were absent or rare. The expression of PDL1 on tumor cells did not correlate with any other immune cells. Expression of PD1 on lymphocytes was frequently encountered. None of analyzed immune cells showed correlation with overall survival. Immune cells in bronchoalveolar lavage and tissue did not correlate. For the first time, a tissue-based analysis of different immune cells in squamous cell and adenocarcinomas of the lung is provided, trying to explain their potential role in tumor development and progression. Discordant numbers of cells with bronchoalveolar lavage are most probably due to the fact that bronchoalveolar lavage reflects the situation in the whole lung, where chronic obstructive lung disease and other conditions are present.
Insights
Immune cells in lung cancer tissues often support tumor growth, with regulatory T cells and M2 macrophages present, while tumor-killing cells are scarce. Immune cell analysis did not correlate with patient survival.
Area of Science:
- Immunology
- Oncology
- Pulmonology
Background:
- Lung cancers, including squamous cell carcinoma and adenocarcinoma, employ diverse immune evasion strategies beyond PD-1/PD-L1.
- Understanding the tumor microenvironment's immune cell composition is crucial for deciphering cancer progression and immune system interactions.
Purpose of the Study:
- To analyze immune cell profiles in lung squamous cell carcinoma and adenocarcinoma tissues and bronchoalveolar lavage (BAL) samples.
- To correlate immune cell phenotypes with tumor progression and overall survival in lung cancer patients.
Main Methods:
- Analysis of immune cell populations in resected tumor tissues and BAL samples from lung cancer patients.
- Correlation of immune cell profiles with clinical data, including overall survival.
- Assessment of specific immune cell types such as T cells, dendritic cells, and macrophages.
Main Results:
- Immune cells within tumor tissues predominantly exhibited a tumor-cooperating phenotype, characterized by high regulatory T cell numbers or VISTA expression on lymphocytes.
- Tumoricidal dendritic cells and M1 macrophages were largely absent, while tumor-promoting M2 macrophages and certain dendritic cell subtypes were prevalent.
- Programmed death-1 (PD-1) expression was frequent on lymphocytes, but PD-L1 on tumor cells did not correlate with other immune cell populations or survival outcomes.
Conclusions:
- Lung tumors create an immunosuppressive microenvironment by promoting tumor-cooperating immune cells and suppressing anti-tumor immunity.
- Immune cell analysis in BAL samples may not accurately reflect the tumor microenvironment due to broader lung conditions.
- Current immune cell markers and BAL analysis showed no correlation with overall survival in this cohort, necessitating further research.
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