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Motohiro Izumi
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P72 - Tumor Biology and Systems Biology - Basic and Translational Science - Tumor Microenvironment (ID 211)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P72.03 - Tumor Microenvironment Disparity in Multiple Primary Lung Cancers (ID 1243)
00:00 - 00:00 | Presenting Author(s): Motohiro Izumi
- Abstract
Introduction
Multiple primary lung cancers (MPLCs) occur from the identical background including immune status and carcinogenic risk factors. Though MPLCs have been reported to harbor various genetic profiles within the same individuals, the differences in tumor microenvironment (TME) among them remain unclear. In this study, we investigated the effects of genetic aberrations, non-intrinsic factors, and histological subtypes on tumor immunity by comparing TME among multiple lesions.
Methods
Seventy-three surgically resected specimens from 32 patients diagnosed as MPLC were analyzed. Written informed consent was obtained from all patients. Clinicopathological features, the patients’ age, sex, smoking history, body mass index, radiologic features and surgical procedures were reviewed. DNAs were successfully extracted from 38 out of 73 tumors and deep-sequenced for somatic mutations in 409 cancer-associated genes. PD-L1 expression on tumor cells (TCs) and immune cells (ICs), CD3-positive tumor infiltrating lymphocytes (TILs), CD8/CD3 ratio, and FOXP3-positive TILs were evaluated by immunohistochemistry. PD-L1 expression was classified as negative (< 1%) and positive (≥ 1%). The number of CD8- and FOXP3-positive TILs, and CD8/CD3 ratio were evaluated on a scale of 0‐2, with 0‐1 as low and 2 as high. The correlation between TME and genetic aberrations, non-intrinsic factors, or histological subtypes was analyzed using chi-squared test or Fisher’s exact test.
Results
PD-L1-positive TCs and ICs were observed in 9 tumors (12.3 %), and 19 tumors (26.0 %), respectively. Concordance rate of PD-L1 expression among MPLCs on TCs and ICs was 75.0% and 62.5%, respectively. There was a significant difference in the concordance rate of the CD8/CD3 ratio between patients with synchronous and metachronous MPLCs, and the other TME had no correlation with chronal difference (PD-L1 expression in TCs, P = 0.646; PD-L1 expression in ICs, P = 1.000; CD3-positive TILs, P = 1.000; CD8/CD3 ratio, P = 0.00796; FOXP3-positive TILs, P = 1.000). PD-L1 positivity in TCs was significantly more frequent in males and medium or heavy smokers (P = 0.00821 and 0.00855, respectively). PD-L1 positivity in both TCs and ICs was significantly lower in EGFR-mutated tumours than wild-type tumours (P = 0.0172 and 0.0209, respectively). The difference in TME even within the same individuals was observed between the KRAS-mutated-only tumor (PD-L1 negative and FOXP3-positive TILs of score 1) and the KRAS and TP53-co-mutated tumor (PD-L1 positive and FOXP3-positive TILs of score 2), and between the KRAS-mutated-only tumor (CD3-positive TILs of score 0; CD8/CD3 ratio of score 2; FOXP3-positive TILs of score 0) and the KRAS and STK11-co-mutated tumor (CD3-positive TILs of score 1; CD8/CD3 ratio of score 0; FOXP3-positive TILs of score 1). Significantly more FOXP3-high TILs (≥ 10 cells/HPF) were observed in invasive histological subtypes than in non-invasive histological subtypes (P = 0.0418). There was no significant difference between pathological subtypes regarding CD3-positive TILs and CD8/CD3 ratio.
Conclusion
Results of the study on TME among MPLCs revealed that never-smokers and females were unlikely to express PD-L1 and confirmed that mutational status was associated with TME. Histological subtypes may have an impact on the efficacy of immune therapy due to its potential correlation with regulatory T cells.
