Virtual Library
Start Your Search
Young Kwang Chae
Author of
-
+
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
-
+
MA 05.11 - Endothelial Adhesion Molecule Overexpression Correlates to Decreased CD8 T Cells and Increased B/Treg Cells in Lung Cancer (ID 8609)
16:55 - 17:00 | Presenting Author(s): Young Kwang Chae
- 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.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.07-025 - Correlating ISEND and Tumor Mutation Burden (TMB) with Clinical Outcomes of Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients on Nivolumab (ID 9587)
09:30 - 09:30 | Author(s): Young Kwang Chae
- Abstract
Background:
We developed an algorithmic model namely, the iSEND (Sex, ECOG performance status, NLR [Neutrophil-to-Lymphocyte Ratio] & DNLR [Delta NLR =NLR posttreatment - pretreatment NLR]) to predict the clinical outcomes of aNSCLC patients receiving nivolumab. Performance of the iSEND has not been compared with other potential immunotherapy biomarkers like TMB.
Method:
We identified 36 aNSCLC patients who received nivolumab after platinum with commercial TMB reports. As described in our previous reports, the iSEND was used to categorize patients into good, intermediate, and poor groups. 36 matched patients were also categorized into high TMB: ≥ 20 m/Mb (mutations per megabase), intermediate TMB: 6-19 m/Mb, and low TMB: ≤5 m/Mb. We evaluated progression free survival (PFS), and overall survival (OS). Performances of the iSEND and TMB were correlated with clinical benefit at 12+/-2 weeks by receiver operating characteristic (ROC) curves.
Result:
The median follow-up was 18.4 months (95% CI: 10.1-26.7). There were 16 deaths. The number of patients from iSEND good, intermediate, and poor groups were 12 (33%), 18 (50%), and 6 patients (16%), respectively. The median overall survivals of iSEND good, intermediate, and poor groups were 15.7 (10.8-20.58), 10.3 (4.8-15.7), and 3.7 (0-7.8) months, respectively (p=0.00006). The median overall survivals for high, intermediate, and low TMB groups were unreached, 10.3 (4.7-15.9), and 12.4 (7.1-17.7) months, respectively. (p=0.211, Figure1) The area under ROC curve of the iSEND for clinical benefit at 12+/-2 weeks was 0.733 (p=0.025, 95% C.I.: 0.56-0.90). Four intermediate iSEND patients who had OS less than 6 months had low TMBs. Figure 1. Kaplan-Meier curves for Overall Survival by iSEND model and TMBFigure 1
Conclusion:
From a limited retrospective single institutional database, iSEND characterized the clinical outcomes of aNSCLC patients on nivolumab well and high TMB correlated with better outcomes. A larger cohort validation is encouraged to explore the mutual supplementary benefit for improved performance.
-
+
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 - 09:30 | Author(s): Young Kwang Chae
- 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.
-
+
P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P3.02-013 - Prognostic Role of Circulating Tumor DNA (ctDNA) and Immune Cell Biomarkers in Non-Small Cell Lung Cancer (NSCLC) (ID 10358)
09:30 - 09:30 | Presenting Author(s): Young Kwang Chae
- Abstract
Background:
Peripheral blood biomarkers can provide valuable information in a relatively non-invasive manner. In solid tumors, it has been suggested that ctDNA mutant allele frequency (MAF) and immune cell counts from peripheral blood complete blood count (CBC) at baseline may be associated with survival outcome. Here, we investigated the role of ctDNA MAF and immune cells as prognostic biomarkers that may predict overall survival in patients with NSCLC.
Method:
A retrospective cohort of 128 patients with ctDNA sample testing performed by ctDNA NGS test (Guardant360) were selected. ctDNA MAF of the dominant clone was collected. CBC’s drawn within a 1-2 week window (baseline) of ctDNA were reported for absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC), neutrophil lymphocyte ratio (NLR) and platelet count. Platelets and MAF were analyzed by quartiles (lower 75% vs highest 25%). Survival analyses and Cox regression analyses were performed on these variables.
Result:
A significant association was found for ANC (hazard ratio (HR) = 1.17, p<0.001), AMC (HR=1.98, p=0.037), MAF (HR=2.53, p=0.005), NLR>5(HR=2.98, p<0.001), and platelet counts (HR=2.49, p=0.006) with overall survival (OS), but not ALC. In multivariate analyses adjusting for clinical variables including age, sex, smoking status, histology, disease stage, number of prior lines of treatment, prior radiation, history of other cancers and ALK/EGFR mutation status, ANC remained as an independent predictor of OS(HR= 1.19, p<0.001). Figure 1
Conclusion:
Higher ANC, AMC, NLR, platelet counts and MAF were associated with poor overall survival. Further studies are required to validate our findings in patients with NSCLC.
