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W.H. Bae
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MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Yoichi Nakanishi, P. Mitchell
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 303 + 304
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MA 05.11 - Endothelial Adhesion Molecule Overexpression Correlates to Decreased CD8 T Cells and Increased B/Treg Cells in Lung Cancer (ID 8609)
15:45 - 17:30 | Author(s): W.H. Bae
- Abstract
- Presentation
Background:
Immunotherapy has become a promising recourse for lung cancer therapy. The endothelium separates circulating immune cells and the tumor microenvironment, and it is necessary for immune cells to penetrate this barrier to accost the tumor. This requires cell-matrix interactions via endothelial adhesion molecules(EAM) such as selectin and integrin. While it is expected that higher expression of EAM is linked to greater immune cell infiltration in general, little is known as to its actual effect on various types of immune cells in human lung cancer.
Method:
Based on the TCGA database, mRNA-seq values of genes related to the leukocyte recruitment cascade were analyzed in 504 patient samples with lung squamous cell carcinoma(SCC) and 522 patient samples with lung adenocarcinoma. The genes were divided into 3 sets: rolling, firm adhesion, and transmigration. Immune cell infiltration of each set was analyzed using Gene Set Enrichment Analysis(GSEA), and p values were derived from Fisher’s exact and Chi-squared tests.
Result:
In lung SCC, overexpression(z score>2.0) of the above genes was statistically significantly correlated with decreased infiltration of activated CD4/CD8 T cells, but increased infiltration of activated B/Treg cells (Figure1). Similar trend was also observed in lung adenocarcinoma. Macrophage, dendritic cells, and natural killer cells showed increased infiltration in the EAM overexpression groups of both SCC and adenocarcinoma. Overall survival showed no significant difference in all three EAM gene overexpression groups in both types of lung cancer.Figure 1
Conclusion:
We demonstrate for the first time that overexpression of EAM genes is linked to differential infiltration of various immune cells (including decreased CD4/CD8 T cells and increased activated B/Treg cells) in human lung cancer tissue. Recruitment of B/Treg cells by EAM may have an impact on inactivation of infiltrated T cells in the tumor microenvironment. This suggests that EAM status may serve as a predictive biomarker for T cell-mediated immunotherapy.
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-043 - Barrier Molecule Overexpression is Associated with Increased CD8 T Cells and Decreased B/Treg Cells in Human Lung Cancer (ID 8617)
09:30 - 16:00 | Author(s): W.H. Bae
- Abstract
Background:
Immunotherapy is an encouraging therapeutic option for lung cancer therapy. For immune cells to interact with tumors, they must first traverse the cell junctions between neighboring cells. While it is expected that higher expression of barrier molecules is linked to lesser immune cell infiltration in general, little progress has been made in our understanding of how these barrier molecules mechanistically interact with immune cells in lung cancer.
Method:
Barrier molecule genes were divided into 3 types: tight junction, adherens junction, and desmosome. mRNA-seq values of each type were analyzed in 504 patient samples with lung squamous cell carcinoma(SCC) and 522 patient samples with lung adenocarcinoma from the TCGA database. Immune cell infiltration of each set was evaluated using Gene Set Enrichment Analysis(GSEA), and p values were analyzed from Chi-squared and Fisher’s exact tests.
Result:
In lung adenocarcinoma, overexpression(z-score>2.0) of desmosome genes significantly correlated with increased infiltration of activated CD4/CD8 T cells, and Th17 cells, but decreased infiltration of activated B cells, mast cells, macrophages, and regulatory T cells(Figure1). There was no significant difference in the immune cell landscape of groups overexpressing desmosome genes in lung SCC. In addition, there was no significant difference in groups overexpressing tight or adherens junction genes in both types of cancer. Overall survival also showed no significant difference in all 3 barrier molecular gene overexpression groups in both types of lung cancer.Figure 1
Conclusion:
Our study demonstrates that elevated barrier molecule(desmosome) gene expression is associated with increased infiltration of cytotoxic CD8 T cells and decreased infiltration of activated B/Treg cells in human lung adenocarcinoma. The inverse association between cytotoxic CD8 T cells and activated B/Treg cells aligns with previous reports of tumor-infiltrating B cells inhibiting T cells. Further investigation is required to understand the roles of barrier molecules and its immune modulatory effect in various types of cancers.
