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Jin Li
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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
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JCSE01.20 - Pilot Study on the Tumor Immune Microenvironment Between Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) (ID 3434)
07:00 - 11:15 | Author(s): Jin Li
- Abstract
Abstract
Background
Tumor immune microenvironment plays an important role in immunotherapy and prognosis. However, the differences and the clinical significance between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) is still largely unknown.
Methods
Resected lung cancer FFPE specimens and matched peripheral blood mononuclear cells (PBMC) from six patients with NSCLC (three adenocarcinoma, three squamous cell carcinoma) and three patients with SCLC were collected. All of the nine patients underwent stage III disease. Tumor mutation burden (TMB) was evaluated by hybridization capture based next-generation sequencing with 1021 cancer associated genes. Tumor infiltrating lymphocytes (TILs) were assessed by immunohistochemistry using multiple immune markers and meanwhile the intratumoral T-cell repertoires were analyzed via high-throughput sequencing of TCR β-chain.
Results
Typical EGFR mutations in adenocarcinoma (2 in 3), NSCLC and RB1 mutations in SCLC (3 in 3) were observed. SCLC patients showed significantly higher TMB than NSCLC. Regarding to the tumor immune microenviroment, SCLC tumors exhibited lower infiltration of CD3+ and CD8+ TILs (P< 0.05). Furthermore, we found that SCLC patients tended to have lower TCR Shannon index (P= 0.167) and higher Clonality index (P= 0.095). Interestingly, patients with higher Shannon index exhibited better Overall Survival (OS) while Clonality was potentially associated with decreased OS. However, further study with more patients is needed to confirm the results.
Conclusion
Tumor immune microenvironment varies between NSCLC and SCLC patients. Specifically, less prevalent and lower diversity of TILs were observed in SCLCs. This might potentially influence survival outcomes.
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MA14 - The Adequate MTarget Is Still the Issue (ID 140)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Diego Signorelli, Juergen Wolf
- Coordinates: 9/09/2019, 15:45 - 17:15, Hilton Head (1978)
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MA14.01 - Clinical and Genomic Features of Chinese Lung Cancer Patients with Germline Mutations (Now Available) (ID 682)
15:45 - 17:15 | Author(s): Jin Li
- Abstract
- Presentation
Background
Recent studies on next generation sequencing (NGS) data from cancer patients have demonstrated that germline mutations in genetic predisposition genes were more common than previous known in many cancer types including lung cancer. However, most previous studies have focused on western patient population and the germline mutation landscape in Asian lung cancer patients and the clinical and genomic features in these patients are largely unknown.
Method
NGS data from a targeted panel of 1,021 known cancer genes from paired cancer and germline DNA of 1,797 Chinese lung cancer patients was analyzed to identify pathogenic or likely pathogenic (P/LP) germline variants in predisposition genes based on American College of Medical Genetics and Genomics (ACMG) 2015 guideline.
Result
Totally, 5.95% of lung patients were found to harbor germline variants in 35 cancer predisposition genes. The prevalence of germline mutations was higher in patients under 40 compared to older counterparts (10.1% vs 5.74%, p=0.103, Chi-Square test ) although it did not reach statistical significance. However, germline BRCA1/2 mutations were associated with earlier age of onset (median 52.5 vs 60 years-old, p=0.0080 by Mann-Whitney test). Furthermore, patients with P/LP germline mutations had significantly more somatic mutations in KRAS (p=0.012, fisher’s exact test) and c-MET (p=0.018, fisher’s exact test) oncogenes, but less in tumor suppressor gene TP53 (p=0.019, fisher’s exact test). Compared to western lung cancer patients enrolled in TCGA, P/LP germline mutations in BRCA2, FANCA, ATM, MUTYH, BLM, TP53, BRCA1, CHEK2, PMS2, NBN and FANCC were identified in both current Chinese cohort and TCGA cohort with BRCA2 germline mutations significantly more common in Chinese cohort than TCGA cohort (p=0.015, Fisher’s exact test). In addition, RAD51D, FANCD2, BRIP1, MSH6, PMS1, PALB2, RAD51C, SDHA, TSC2, BAP1, CDH1, FLCN, NF1 and RUNX1) were exclusively identified in Chinese patients, while RET, ERCC3, FANCG and VHL were only detected in TCGA cohort.
Conclusion
These results implied that there might be both common and unique cancer predisposition germline mutations for lung cancer between Asian and Western patient populations.
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P1.12 - Small Cell Lung Cancer/NET (ID 179)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.12-10 - The Genomic Profiles of Small Cell Lung Cancer in East Asian (Now Available) (ID 1608)
09:45 - 18:00 | Author(s): Jin Li
- Abstract
Background
Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with poor survival, which is initially effective treated by chemotherapy and relapses rapidly. Comprehensive genomic analysis of SCLC contribute to the understanding of drug resistance mechanisms and discerning patients who respond to treatments, especially immunotherapy that has been proved to be efficient in SCLCs harboring high tumor mutational burden (TMB). This study was initiated to investigate the genomic profiles of SCLC in Chinese.
Method
SCLC specimens were obtained by surgery or biopsy from 64 patients. Whole-exome sequencing (WES) was performed on tumor samples without paired PBMCs. Alterations were confirmed with VAF between 5% and 90%, subsequently filtered by mutated genes above 5% in J.Geroge’s and LY. Jiang’s researches. Tumor mutational burden was calculated by the number of non-synonymous mutations. The mutations of highly mutated driver genes in SCLC was also determined based on MH. Bailey’s study.
Result
TP53 and RB1 were the most frequently mutated genes in SCLCs, occurred in 87.5% (56/64) tumors, and furthermore related to a higher mutational burden (P = 0.0008 and 0.0274, respectively). Tumor mutational burden after filtered by highly mutated genes in SCLC was 333 non-synonymous mutations per tumor, with high mutation rates exhibited in advanced stage of SCLCs, while the smoking history did not correlate with the number of mutations. Driver genes mutation in high frequency was detected almost in all tumors (63/64), with 17.4 mutations on average (0-144). Tumors with POLE mutation tended to harbor a higher driver genes mutation rates, as well as a higher TMB. Pathway analysis using altered driver genes showed enrichment of PI3K-Akt (adj. P = 8.38e-07), MAPK (adj. P = 1.63e-05), mismatch repair (adj. P = 4.55e-05), cell cycle (adj. P= 0.0016), and Wnt (adj. P= 0.0047) signaling pathways. We did not observe significant correlation of mutations in Wnt signaling pathway with survival, though it has proved to be a mechanism of chemoresistance in SCLCs.
Conclusion
SCLCs exhibited complex genomic features with extensive mutational burden and high numbers of altered driver genes. Various sorts of cancer-related pathways were enriched, highlighted the complicacy of SCLCs.
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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
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-17 - Immune Repertoire Is a Potential Predictive Biomarker for Evaluating the Efficacy of Mutant Neoantigen Specific T Cell Combined with PD1 Antibody (Now Available) (ID 555)
10:15 - 18:15 | Author(s): Jin Li
- Abstract
Background
The efficiency of PD1 monoclonal antibody used alone is not satisfactory. The therapeutic method of solid tumor with mutant neoantigen specific T (Nas-T) cell developed in this study is an adoptive cell therapy which is specific for each patient. Our previous research has proved that Nas-T can prolong patients' PFS with a good safety. We aim to further explore the effect of Nas-T on OS and to evaluate the characteristics of immune repertoire (IR) as a predictive biomarker.
Method
A total number of 12 patients with advanced solid tumors who failed after multiline treatments were recruited. They were treated with Nas-T cells, PD1 antibody and BSC; other 11 patients were treated with PD1 inhibitors and BSC as control. Peripheral blood was collected at baseline and per cycle (21-28d) respectively. Immunosequencing of the CDR3 regions of human TCRβ chains was used to detect IR. T-cell diversity and clonality for each IR was calculated. To quantitatively evaluate the consistency of the infused T-cell repertoires during the therapy, we adopted the Morisita overlap index (MOI), which considers the composition and the abundance of T-cell rearrangements. MOI ranges from 0 to 1, with 1 indicating identical TCR repertoires and 0 indicating completely distinct TCR repertoires between two samples.
Result
Conclusion
Updated data showed there was no statistical significance in OS (P>0.05), which may be related to the small sample size and short follow-up time. Compared to baseline, T-cell repertoire of NCB and DCB after 1st cycle displayed significant changes: Shannon 0.96 vs 1.20, P=0.004; Clonality 1.20 vs 0.64, P=0.003. Elevated Clonality may indicate expanded tumor-specific T-cells which could recognize mutant neoantigen specifically. MOI result for one patient, for example, exhibited a good consistency among each batch of infused Nas-T.
The combined immunotherapy of mutant Nas-T cell and PD1 antibody is more effective than PD1 antibody alone in prolonging PFS, but has no effect on OS. IR Clonality change shows its potential as a predictive biomarker.
