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Jie Wang
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ES14 - Novel Immunotherapy Strategies in NSCLC (ID 184)
- Event: WCLC 2020
- Type: Educational Session
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 11:45 - 12:45, Scientific Program Auditorium
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ES14.06 - Novel Immunotherapy Targets in NSCLC (ID 4014)
11:45 - 12:45 | Presenting Author(s): Jie Wang
- Abstract
Abstract not provided
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MA01 - Novel Systemic Treatment in NSCLC (ID 102)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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MA01.03 - The Role of Gut Microbiome in the Efficacy of Chemotherapy in Patients With Locally Advanced and Advanced Lung Cancer (ID 1598)
11:45 - 12:45 | Author(s): Jie Wang
- Abstract
- Presentation
Introduction
Accumulating evidences have disclosed the important role of gut microbiome in modulating response of immunotherapy in the patients with lung cancer. However, research exploring the relationship of intestinal flora and chemotherapy is still limited. The study is to investigate the correlation between intestinal flora and chemotherapy efficacy in locally advanced and advanced lung cancer.
Methods
We analyzed baseline stool samples from lung cancer patients before chemotherapy treatment, through metagenomics of gut microbiota. The composition, diversity, function and metabolic pathway of microbial communities were compared among patients with different chemotherapy response.
Results
From September 1, 2018 to September 30, 2019, 64 consecutive lung cancer patients treated with chemotherapy were included into this study. All patients provided the stool samples. 33 of 64 patients responded to treatment (responders) and another 31 patients didn’t (non-responders). The median progression-free survival was 7 months (range, 1.5-14.5). Streptococcus_mutans (P=0.026) and Enterococcus_casseliflavus (P=0.049) were enriched in responders, while 11 bacteria including Leuconostoc_lactis (P=0.002) were enriched in non-responders. Functional analysis of metabolic pathways revealed that L-glutamate degradation VIII pathway was enriched in responders (P=0.014), and 3 pathways including C4 photosynthetic carbon assimilation cycle were enriched in non-responders (P<0.05). Patients enriched with 5 bacterial species, such as Turicibacter_sanguinis (P=0.008) had longer progression-free survival than those enriched in the 7 bacteria including Streptococcus_anginosus (P=0.013) (HR, 0.189; 95% CI, 0.092-0.387; P< 0.0001). Purine nucleobases degradation I and other 4 metabolic pathways were enriched in lung cancer patients with longer progression-free survival (P<0.05). In addition, significant associations of certain bacterial species with clinical parameters such as pathological pattern were observed by spearman correlation analysis.
Conclusion
The study indicated that specific intestinal bacteria may be associated with the clinical outcome of locally advanced and advanced lung cancer patients with chemotherapy, which need to be validated by prospective and large samples studies.
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P59 - Tumor Biology and Systems Biology - Basic and Translational Science - Genomics (ID 197)
- 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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P59.07 - Molecular Profiling of Human Non-Small Cell Lung Cancer by Single-Cell RNA-Seq (ID 2032)
00:00 - 00:00 | Presenting Author(s): Jie Wang
- Abstract
Introduction
Lung cancer is one of the malignant tumors with the highest morbidity and mortality worldwide. As the lung is a complex organ composed of more than 40 different types of cells, which contribute to the heterogeneity of lung cancers at tumor initiation, it is important to separate different cell types to profile their characteristics. In this study, we aim to comprehensively analyze the molecular heterogeneity of non-small-cell lung cancer (NSCLC).
Methods
We performed single-cell RNA-seq analyses on 7,364 individual cells from tumor tissues and matched normal tissues from 19 primary lung cancer patients and 1 pulmonary chondroid hamartoma patient.
Results
We identified a significant proportion of cancer cells simultaneously expressing classical marker genes for two or three histologic subtypes of NSCLC—adenocarcinoma (ADC), squamous cell carcinoma (SCC), and large cell neuroendocrine carcinoma (LCNEC) in the same individual cell; this was verified by coimmunostaining and RNA in situ hybridization. These data suggest that mixed-lineage tumor cells are highly plastic with mixed features of different types of NSCLC. Both copy number variation (CNV) patterns and mitochondrial mutations clearly showed that the mixed-lineage and single-lineage tumor cells from the same patient had common tumor ancestors rather than different origins. Moreover, we revealed that patients with high mixed-lineage features of different cancer subtypes had worse survival than patients with low mixed-lineage features, indicating that mixed-lineage tumor features were associated with poorer prognosis. Based on the pseudotime trajectory of gene expression dynamics from normal epithelial cells to cancer cells, a cancer-specific gene set has been identified, which includes AKR1B1 and RAMP1. Knockdown experiments verified that both AKR1B1 and RAMP1 were necessary for tumor growth, suggesting that they can serve as candidate targets for tumor therapy.
Conclusion
Our work provides novel insights into the heterogeneity of NSCLC and offers clues for the more refined classification, diagnosis and treatment of each subtype.
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P60 - Tumor Biology and Systems Biology - Basic and Translational Science - Immune Bio (ID 198)
- 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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P60.03 - Identifying Patterns in Responses to PD-1 Immunotherapy for Patients With Squamous Cell Lung Cancer and Non-Squamous Cell Lung Cancer (ID 1537)
00:00 - 00:00 | Author(s): Jie Wang
- Abstract
Introduction
Lung cancer is associated with high morbidity and mortality, yet the emergence of immunotherapies offers hope for those in treatment. Research in this field has recently identified subtle differences in the efficacy of PD-1 monotherapy in patients with histologies of squamous cell lung cancer (LUSC) and non-squamous cell lung cancer (non-LUSC). Therefore, mapping different responses to PD-1 immunotherapy may pave the way to more individualized treatments and enhance the effect of interventions. Here, we aimed to identify the underlying mechanisms involved in PD-1 immunotherapy responses in patients with LUSC and non-LUSC.
Methods
We obtained expression profiles from 35 patients (GSE93157) who received PD-1 immunotherapy from the Gene Expression Omnibus (GEO) database. By using hallmark gene sets and all curated gene sets as references, we performed Gene Set Enrichment Analysis (GSEA) between responders and non-responders with LUSC and compared findings with the non-LUSC sample. A nested comparison using the following algorithm: (LUSC_response vs. LUSC_non-response) versus (non-LUSC_response vs. non-LUSC_non-response) was performed, setting the significance threshold to p < 0.05 and the log2 Foldchange to >1.0 in order to identify differentially expressed genes (DEGs). Functional annotation was performed using DAVID 6.8 online tool.
Results
GSEA results revealed that the enrichment of epithelial mesenchymal transition (EMT) signaling pathway is significant, positively correlating with responses to PD-1 immunotherapy in patients with LUSC. By contrast, patients with non-LUSC who received EMT signalling pathway enrichment showed no response to PD-1 treatment. Additionally, the IL4 pathway appears to be significant in PD-1 immunotherapy responses. Both LUSC and non-LUSC patients showed improved responses to PD-1 treatment when the IL4 pathway was upregulated. Nested comparisons identified 12 DEGs within our sample of LUSC and non-LUSC patients, which might provide reasons for the different responses to PD-1 immunotherapy. Gene Ontology (GO) term analysis also indicates that the 12 DEGs significantly correlate with immune responses, lymphocyte activation, B cell activation, cytokine activity, and chemokine activity.
Conclusion
Through data mining, we identified different PD-1 immunotherapy response patterns in patients with LUSC and non-LUSC, including EMT signaling and IL4 pathways. We also identified 12 DEGs as PD-1 response-related genes which require further investigation but may influence both LUSC and non-LUSC patient prognoses.
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P78 - Immunotherapy (Phase II/III Trials) - Immune Checkpoint Inhibitor Single Agent (ID 255)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P78.03 - Camrelizumab Umbrella Trial Based on PD-L1 Expression: OS and PFS2 in Pre-Treated Advanced NSCLC (ID 1453)
00:00 - 00:00 | Author(s): Jie Wang
- Abstract
Introduction
In a phase II umbrella study (NCT03085069), camrelizumab (a potent anti–PD-1 monoclonal antibody) demonstrated promising efficacy and manageable safety profile as second-line treatment in advanced/metastatic NSCLC. Patients with higher PD-L1 expression derived greater benefit from camrelizumab. Here we present an updated OS, PFS, and PFS2 based on longer follow-up.
Methods
Patients who had progressed during or following platinum-based doublet chemotherapy were enrolled and assigned to 4 cohorts according to PD-L1 tumor proportion score (TPS) to receive camrelizumab at 200 mg IV Q2W. Patients with EGFR or ALK alterations who had progressed on at least one approved tyrosine kinase inhibitor and with PD-L1 TPS ≥50% were eligible. PFS2 was defined as time from first dose of camrelizumab to objective tumor progression on next-line treatment or death from any cause, whichever occurred first.
Results
From May 24, 2017 to Aug 1, 2018, 146 patients were enrolled. As of data cutoff on Jan 31, 2020, the median follow-up was 22.9 months (95% CI 21.7–24.2). Median OS and PFS was 14.8 months (95% CI 10.3–18.8) and 3.2 months (95% CI 2.0–3.4), respectively. Third-line therapy and beyond was received by 65 (44.5%) patients. PFS2 was 10.0 months (95% CI 8.2–12.4). Subgroup analysis showed that patients with positive PD-L1 TPS commonly had longer PFS and PFS2 (Table 1). No new safety signal with camrelizumab was identified.
Table 1 Survival of camrelizumab in PD-L1 TPS subgroups
Population No. of patients OS (months), median (95% CI) PFS (months), median (95% CI) PFS2 (months), median (95% CI) PD-L1 TPS <1% 74 9.2 (6.5–15.4) 2.1 (1.9–3.2) 7.5 (5.7–8.9) PD-L1 TPS ≥1% 72 23.3 (13.2–NR) 3.8 (2.0–7.2) 16.6 (10.2–19.8) PD-L1 TPS 1–49% 42 NR (14.8–NR) 3.4 (1.8–6.0) 16.9 (10.2–20.4) PD-L1 TPS ≥50% (without EGFR alterations) 25 23.3 (9.0–NR) 7.6 (2.0–16.8) 18.7 (9.0–26.8) PD-L1 TPS ≥50% (with EGFR alterations) 5 10.3 (1.2–NR) 1.7 (1.2–NR) 9.8 (1.2–16.6) ITT 146 14.8 (10.3–18.8) 3.2 (2.0–3.4) 10.0 (8.2–12.4) NR, not reached.
Conclusion
The updated results demonstrated improved survival compared with historical data of the second-line chemotherapy. Patients with positive PD-L1 expression derived greater benefit from camrelizumab. These data supported the long-term outcome of camrelizumab as the second-line therapy in advanced/metastatic NSCLC.
