초록접수 현황
| 17F-249 | 구연 미채택시 포럼 발표 |
Prominent Immune Suppressive Tumor Microenvironment in Female Never-smoker Lung Cancer Patients with EGFR Mutations
Byung-Jo Park, Da-Eun Ryu, Yong Soo Choi, Hong Kwan Kim, Jong Ho Cho, Jung Hee Lee, Jinseon Lee, Hae-Ock Lee, Je-Gun Joung, Woong-Yang Park, Jhingook Kim
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Purpose : According to genetic and genomic analysis as well as previous clinical research, lung cancer in never-smokers might have pathogenesis and progression different from that of lung cancer among smokers. There has been indirect evidence that different types of mutations in tumors might be related to the altered immune functions.
Methods : Tissues from 108 female patients with lung adenocarcinoma (never-smokers: 101 & smokers: 7) at our institution, were analyzed by next-generation genomic sequencing including whole-exome seq and RNA-seq. Somatic mutations and gene expression levels of immune signature genes were profiled.
Results : Female never-smoker adenocarcinoma was significantly associated with low level of cytotoxic-cells, NK-cells, mast-cells and neutrophils, in contrast with high level of B-cells and regulatory T-cells. The data suggest that cells of cytotoxic functions are deactivated, whereas cells of immune suppressive functions are activated in female never-smoker adenocarcinoma. Especially, the expression of immune markers specific for B-cells, regulatory T-cells, mast-cells and dendritic-cells was up-regulated in tumors from patients with EGFR mutation, its mutation status may play an important role in augmenting the immune suppressive activity. EGFR mutation–positive adenocarcinoma was significantly associated with low level of expression of an immune checkpoint molecule, programmed death-ligand 1 (PD-L1), in contrast with high level of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte–associated antigen 4 in female never-smokers.
Conclusion : This overall immune suppression in lung adenocarcinoma patients with EGFR mutation might explain the lower response rate of anti-PD-1/PD-L1 blockade to the female never-smokers, which suggests that other approaches to block the immune suppressive microenvironment would be necessary.
Methods : Tissues from 108 female patients with lung adenocarcinoma (never-smokers: 101 & smokers: 7) at our institution, were analyzed by next-generation genomic sequencing including whole-exome seq and RNA-seq. Somatic mutations and gene expression levels of immune signature genes were profiled.
Results : Female never-smoker adenocarcinoma was significantly associated with low level of cytotoxic-cells, NK-cells, mast-cells and neutrophils, in contrast with high level of B-cells and regulatory T-cells. The data suggest that cells of cytotoxic functions are deactivated, whereas cells of immune suppressive functions are activated in female never-smoker adenocarcinoma. Especially, the expression of immune markers specific for B-cells, regulatory T-cells, mast-cells and dendritic-cells was up-regulated in tumors from patients with EGFR mutation, its mutation status may play an important role in augmenting the immune suppressive activity. EGFR mutation–positive adenocarcinoma was significantly associated with low level of expression of an immune checkpoint molecule, programmed death-ligand 1 (PD-L1), in contrast with high level of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte–associated antigen 4 in female never-smokers.
Conclusion : This overall immune suppression in lung adenocarcinoma patients with EGFR mutation might explain the lower response rate of anti-PD-1/PD-L1 blockade to the female never-smokers, which suggests that other approaches to block the immune suppressive microenvironment would be necessary.
책임저자: Jhingook Kim
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
발표자: Byung-Jo Park, E-mail : skddls05@gmail.com