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Venessa Chin
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P37 - Pathology - Biomarker Testing (ID 107)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P37.19 - Activin-A and GDF-11 as Predictive Biomarkers for Platinum Response in Non-Small Cell Lung Cancer (ID 762)
00:00 - 00:00 | Author(s): Venessa Chin
- Abstract
Introduction
Lung cancer is the leading cause of cancer death in Australia with 13,000 new cases per year. Although targeted therapy and immunotherapy have drastically changed the treatment landscape, the majority of patients will receive platinum-based chemotherapy for which the response rate is approximately 30% (Reck et al, 2016). An immunohistochemistry-based, predictive biomarker would be beneficial for patients and help avoid toxicity for patients unlikely to respond. 3 potential biomarkers identified in a paper by Marini et al (2018) – activin A, growth differentiation factor-11 (GDF-11) and transforming growth factor-b (TGF-B) –were investigated in a real-world retrospective cohort to determine their relation to objective radiological response and overall survival (Marini et al, 2018).
Methods
We identified 101 patients with advanced non-small cell lung cancer who received platinum chemotherapy at 2 cancer centres between 2014-2015. Archival formalin-fixed paraffin embedded tissue samples were stained with activin A and GDF-11. Slides were manually scored by 2 independent clinicians including a specialist pathologist using the multiplicative quickscore method, which multiplies the percentage of tumour cells and intensity staining of 0-3+ to create a score out of 18 (Detre et al, 1995). We performed Kaplan Meier analysis and a Cox-proportional hazards model for confounding variables using R software to analyse the relationship between high immunohistochemistry scores (greater than the median score) and overall survival. A chi square analysis was performed to analyse the relationship between immunohistochemistry expression and objective radiological response.
Results
We performed statistical analysis around the median cytoplasmic score for Activin-A (6) and GDF-11 (12). The overall median survival was 15.3 months. No significant difference in survival was detected between the two populations for Activin-A (p value = 0.97) or GDF-11 (p=0.67). The immunohistochemistry score was also not associated with rates of partial response for Activin A (p value = 0.98) or GDF-11 (p=0.56). Rates of progressive disease were also not associated with high levels of expression of Activin-A (p value 0.22) or GDF-11 (p=0.12).
Conclusion
Despite an association with lower progression-free survival in a retrospective cohort in a previous study, high expression of activin and GDF-11 does not appear to predict for platinum response or overall survival in the setting of non-small cell lung cancer. Further research into TGF-B is in progress.
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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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P60.01 - Single-Cell Transcriptomics to Assess Response to Immunotherapy in Advanced Lung Cancer ex-vivo: Developing a Functional Predictive Assay (ID 881)
00:00 - 00:00 | Presenting Author(s): Venessa Chin
- Abstract
Introduction
Treatment with immunotherapy (IO) has lead to improvements in survival for patients with advanced lung cancer (ALC) but robust predictive biomarkers remain elusive. Single cell genomics provides an opportunity to study cellular profiles in exceptional detail. Novel transcriptomic (scRNA-seq) including VDJ sequencing, allow evaluation of cellular responses to IO in real-time, providing an opportunity for a predictive test.
Methods
Fine needle aspirates taken from patients with ALC are exposed to IO or control invitro. Cells are collected, captured and sequenced using the 5’ VDJ kit (10X Genomics). Cellular subtypes are delineated and phenotyped using Seurat software. Comparisons between the control and treated conditions are conducted. Immunoactivation is measure and correlated with patient response.
Results
4/21 samples have been sequenced. ~5000 cells are sequenced per capture. Cell clustering demonstrates the innate and adaptive immune system and ~10 cancer subtypes per sample. Figure 1 shows diverse cell populations seen. Within the CD8 t-cell population, 3 distinct cytotoxic t-cell subsets are identified; fully functional, pre-exhausted and exhausted.
Figure 1
Conclusion
Using scRNA-seq with VDJ sequencing, the functional capacity of effector cells can be ascertained within the tumour microenvironment and immune cell responses to immunotherapy can be measured. Single cell sequencing has the potential to be used as a functional, predictive assay for treatment with IO.
