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S.H.Y. Kung
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MA 10 - Immunotherapy I (ID 664)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:S. Wang, Robert Pirker
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 303 + 304
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MA 10.09 - Increased T Follicular Helper Cell Infiltration in Lung Adenocarcinoma Tertiary Lymphoid Organs (ID 8487)
11:00 - 12:30 | Author(s): S.H.Y. Kung
- Abstract
- Presentation
Background:
T follicular helper cells (Tfh) are an antigen-experienced CD4+ T cell subset that have been found to play crucial roles in the development of humoral immunity. In particular, their presence in the B cell-rich germinal centre of secondary and tertiary lymphoid tissue aids in B cell maturation through selection of B cells producing high-affinity antibodies. Tfh cells have known roles in autoimmune disease and B cell malignancies; however, their role in many solid tumours, including those of the lung, remains unclear.
Method:
We analyzed 83 paired tumour-normal lung adenocarcinoma samples from the BC Cancer Agency (BCCA) as well as 576 unpaired samples from The Cancer Genome Atlas (TCGA). Relative immune cell content was obtained from gene expression data using a linear support vector regression deconvolution approach (CIBERSORT). Spatial positioning of B and T cells within selected tumour sections was examined through IHC. The impact of Tfh infiltration on patient survival was analyzed using a Cox Proportional Hazard model.
Result:
T follicular helper cells are increased in tumour tissue, accompanied by global upregulation of Tfh markers PDL1 and CXCR5 in both the BCCA and TCGA cohorts. Histological analysis revealed localization of Tfh cells within tertiary lymphoid organs, with direct contact with B cells in the follicular zone observed. Importantly, Tfh recruitment appears to be an early event in tumour development and a function of neoantigen exposure, indicative of an active anti-tumour response rather than a result of chronic inflammation of the tumour microenvironment.
Conclusion:
T follicular helper cells are required for B cell maturation and subsequent antibody responses. As such, it is not surprising that Tfh infiltration in tumour-resident ectopic lymphoid structures correlates with patient survival in various cancer types. Given the importance of tumour-specific antibody responses in natural and therapeutic immunity, further investigation of Tfhs may show prognostic utility and be a marker of early-stage lung tumours.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-038 - Imaging Platform for the Quantification of Cell-Cell Spatial Organization within the Tumour-Immune Microenvironment (ID 9605)
09:30 - 16:00 | Author(s): S.H.Y. Kung
- Abstract
Background:
The contribution of the tumour-immune microenvironment to tumour progression and patient outcome has become increasingly evident. Newly developed genomic tools have enabled the study of immune cell composition from bulk tumour data. However, such tools (e.g. CIBERSORT) do not provide the key spatial information that is crucial to understand tumour-immune cell interactions. To this end, we have developed a multispectral imaging platform that improves upon traditional analysis methods of cell segmentation and cell density calculations by further quantifying nearest-neighbour interactions (cell-cell spatial relationships). We apply this technology to investigate tumour-immune cell spatial relationships and their clinical significance to discover novel biological insights.
Method:
Whole tissue sections from 20 lung adenocarcinomas were stained for CD3, CD8, and CD79a and counterstained with haematoxylin. Multispectral images were acquired for five fields of view and analyzed to quantify cell types. Regions of Interest (ROIs) were then identified for the characterization of intra-tumoural and dense inflammatory regions. Image files including ROIs were analyzed in order to quantify cell-cell spatial relationships. Non-random patterns of immune cell distributions were identified using the Monte Carlo re-sampling method (500 iterations). Immune cell counts, densities, spatial relationships, and significant immune cell distributions were associated with clinical features by two-group comparison (Kruskal-Wallis p<0.001).
Result:
Our analysis generated 234 image files for analysis, including ROIs. Each field of view contained an average of 16,400 cells. The densities of intra-tumoural CD3+CD8+ and CD3+ T cells were significantly lower in recurrent cases, agreeing with literature reports. Following Monte Carlo analysis, non-random cell-cell spatial proximities emerged that were not observed at a cell density level. For example, an increased proximity of CD3+ T cells and B cells was observed in never smokers, while a decreased proximity was observed in ever smokers.
Conclusion:
While immune cell densities are of clinical prognostic importance, their spatial organization within the tumour architecture is of functional importance (e.g. the inhibition of cytotoxic T cell activity by adjacent PD-L1 expressing cells). In addition to cell densities, our platform is capable of quantifying cell-cell spatial relationships, thereby providing further information for clinical associations and for the identification of novel prognostic interactions. This automated quantification could be used to complement visual diagnostics and improve prognostic interpretation of histology specimens.
