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Wei Li
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MA04 - Models and Biomarkers (ID 122)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:Montse Sanchez-Cespedes, Kwok-kin Wong
- Coordinates: 9/08/2019, 13:30 - 15:00, Interlaken (1988)
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MA04.02 - Molecular Profiling of Adenocarcinoma and Squamous Cell Lung Cancer at Single Cell Resolution (Now Available) (ID 1358)
13:30 - 15:00 | Author(s): Wei Li
- Abstract
- Presentation
Background
Adenocarcinoma and squamous are two main subgroups of lung cancer: adenocarcinoma (ADC) accounts for 30-50% and squamous cell carcinoma (SCC) accounts for nearly 30% of all cases respectively. ADC and SCC have different pathological phenotypes and respond differently to various therapies, including immunotherapy. However, the underlying molecular mechanism of such differentiated drug responses still needs to be further characterized.
Method
To achieve high resolution of both tumor cells and their tumor microenvironment (TME), we used single cell RNA sequencing method to characterize ADC and SCC tumors from Stage IV NSCLC patients. Tissue biopsy samples from 21 patients (12 patients with ADC, 9 with SCC) were collected. For each sample, single cell RNA sequencing was performed on an average of 1930 cells. A graph-based clustering approach was used to classify cells into different cell types based on their gene expression patterns. The cellular subtypes of both cancer cells and TME in ADC and SCC samples were analyzed.
Result
ADC and SCC show distinct patterns at single cell resolution. Cancer cells from all ADC patients form two closely related clusters, while cancer cells from SCC patients show high intra-and inter-patient heterogeneity. Gene Ontology (GO) analysis demonstrated that ADC samples are enriched in genes of neutrophil degranulation and activation, while SCCs are enriched in genes related to epidermal cell differentiation and glutathione metabolic process. Genes related to cancer progression and metastasis, such as LSD1 and FASCIN, are normally expressed at higher level in SCC than in ADC. Furthermore, ADC samples contain higher percentage of a specific myeloid cell population, while SCC has higher percentage of fibroblasts, demonstrating the difference also in TMEs of ACD versus SCC.
Conclusion
The significantly higher level of heterogeneity for SCC can be a possible reason for poor responses to standard lung cancer therapies, including immunotherapy. Accurate characterization of SCC with single cell resolution could hold the key to more effective therapeutic strategies.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-57 - Predictive and Prognostic Value of CTC Monitoring in Advanced NSCLC Patients Treated with Immune Checkpoint Inhibitors (ID 1165)
10:15 - 18:15 | Author(s): Wei Li
- Abstract
Background
Immune checkpoint inhibitors (ICI) have recently emerged as a treatment option for selected patients with advanced non-small-cell lung cancer (NSCLC). However, there is a lack of effective biomarker to predict the treatment response and monitor disease progression. In this prospective observational study, we aimed to investigate the predictive and prognostic value of folate receptor-positive circulating tumor cell (FR+CTC), a well-established lung cancer biomarker, in advanced NSCLC patients treated with ICIs.
Method
Advanced NSCLC patients with at least one measurable lesion and expected to undergo ICIs treatment were recruited. Peripheral blood samples were collected from each participant at baseline, after each cycle of ICI treatment, and on disease progression. FR+CTCs were enumerated by using negative enrichment and ligand-targeted polymerase chain reaction methods. Treatment efficacy was analyzed according to the iRECIST criteria. The correlation of FR+CTC level and its dynamic changes with radiological responses was evaluated.
Result
Of the 35 patients, 17 received first-line treatment, 10 received second-line treatment, and 8 received third-line treatment or above. CTCs were detected (≥8.7FU/3ml) in 80.0% of patients at baseline. The baseline CTC of first-line/second-line therapy patients was significantly higher than that of third-line and above therapy patients (median values 16.68 vs 8.36, P=0.017). Meanwhile, there was no significant difference in baseline CTC values between different pathological subtypes and whether PD-L1 was expressed or not. For the radiological responses, after at least two cycles of ICI treatment, PR, SD, and PD were found in 10, 8, and 4 patients, respectively. The CTC count in the PD group at baseline was significant higher than that of the disease control (PR+SD) group (P=0.033). Similarly, the CTC value after two cycles of ICI treatment in PD group (17.84 ± 7.03) was higher than SD/PR group (12.50 ± 4.94), but not statistically significant (P=0.081). However, the changes of CTCs after one or two cycles of immunotherapy were poorly related to the treatment response (P>0.05), perhaps because of the polarization trend of CTC changes in the PR group after treatment.
Conclusion
In sum, these data confirm the predictive significance of CTCs in advanced NSCLC patients treated with immune checkpoint inhibitors. The baseline CTCs value correlated significantly with radiological response. Further studies are needed to confirm whether CTCs can be used as a prognostic factor for advanced non-small cell lung cancer.
