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Paweł Krawczyk
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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: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P60.02 - Insight Into Intestinal Microbiome in NSCLC Patients: More Personalized Immunotherapy in the Crosshairs (ID 1344)
00:00 - 00:00 | Author(s): Paweł Krawczyk
- Abstract
Introduction
Intestinal bacteria are associated with the functioning of the immune system. The composition of the intestinal microbiome may be associated with the effectiveness of anti-PD-1 or anti-PD-L1 immunotherapy in patients with cancers including non-small cell lung cancer (NSCLC).
Methods
We investigated (from September 2018 to December 2019) fecal samples taken prior to immunotherapy with anti-PD-1 or anti-PD-L1 antibodies from 26 NSCLC patients. In 17 (65%) patients adenocarcinoma and in 9 (35%) squamous cell carcinoma was diagnosed.
We isolated DNA from fecal samples and conducted a microbiome analysis using next generation sequencing (NGS) with utility of Illumina MiSeq device. The 16S rRNA metagenomics profiling was made using Qiime 2.0 software. Statistic were conducted with MedCalc software.
Results
Eighth (31%) patients had disease stabilization, 4 (15%) partial response and 14 (54%) disease progression. Higher percentage of Clostridiaceae 1 and Streptococcaceae was observed in patients with disease progression compared to patients with stable disease or partial response to immunotherapy (p=0.007 and p=0.06 respectively).
Median of progression free survival (PFS) in studied group treated with immunotherapy (pembrolizumab, nivolumab or atezolizumab) was 20 weeks (95%CI: 8.0 – 72.0). We observed significant higher risk of disease progression in patients with high burden of Micrococcaceaes, Streptococcaceae and Clostridiaceae 1 compared to patients without presence of this bacteria in fecal samples (HR=0.3061, 95%CI: 0.0893-1.0489, p=0.05; HR=0.1605, 95%CI: 0.0470-0.5484, p=0.0035 and HR=0.1849, 95%CI: 0.0518-0.6601, p=0.0093, respectively).
Conclusion
Our pilot study showed that composition of fecal microbiome, especially high burden of Micrococcaceaes, Streptococcaceae and Clostridiaceae, could influence the effectiveness of immunotherapy in NSCLC patients.
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P60.05 - Influence of Different Concentrations of Nivolumab on T Cell Activation in Patients with Non Small Cell Lung Cancer: in Vitro Study (ID 1924)
00:00 - 00:00 | Presenting Author(s): Paweł Krawczyk
- Abstract
Introduction
Nivolumab is a PD-1 protein inhibitor. Tumor uses PD-1/PD-L1 pathway for escaping from host’s immune surveillance. Nivolumab is used in clinical practice for the immunotherapy of NSCLC patients, but the only one predictive factor is the level of PD-L1 protein expression on the tumor cells. However, data from clinical studies indicates that a positive response for anti-PD-1 treatment is not always correlated with high PD-L1 expression. The aim of our study was to analyse the effect of nivolumab on proliferation and activation of T lymphocytes.
Methods
The study was conducted in group of NSCLC patients in stage IIIB/IV, before starting systemic treatment. CD14+ monocytes and T lymphocytes were isolated from patients' peripheral blood. CD14+ monocytes were used to obtain mature dendritic cells capable of antigen presenting. A 5-day culture was carried out using IL-4 (500 IU/ml), GM-CSF (1000 IU/ml), TNF-α (50 ng/ml ) and 50 ng/ml of tumor peptides (MAGE-A3, MUC-1.2, MUC-1.1). Then, DC’s were cultured for a further 48 hours with autologous T lymphocytes (in rate 1:10) and with the following concentrations of nivolumab: 10, 30, 60 and 90 μg of antibody per 1 ml of culture medium. After that, cytometric analysis of the T cell phenotype was performed.
Results
A significant increase in the percentage of cytotoxic T cells expressing the early activation marker, CD25, was observed in all probes compared to unstimulated culture. In contrast, in T helper cell population, that effect was observed only at 10 μg/ml dose of nivolumab (p = 0.0076). No significant differences were observed in both T cell populations with CD69 and CD95 expression. A significant increase in the percentage of CD8-positive cells with CD107a expression was observed in all tested doses of nivolumab compared to unstimulated culture. Percentage of T helper lymphocytes with IL-4 receptor expression (cells CD124-positive), was significantly higher in the 10 μg/ml dose of nivolumab compared to the control culture (p = 0.0328). In contrast, a significant increase in the percentage of T helper lymphocytes with IL-12 receptor expression was observed in culture stimulated with 30 μg/ml of nivolumab compared to 10 μg/ml dose (p = 0.0208) and in culture stimulated with 60 μg/ml of nivolumab compared to 10 μg/ml dose (p = 0.0218).
Conclusion
Anti-PD-1 antibodies can significantly affect the activation process of T lymphocytes, and in particular enhance the natural cytotoxicity of CD8-positive T cells and direct the differentiation of helper T cells toward Th1 cells. This activity was observed at the lowest concentration of nivolumab. The results of the experiment can be practically used to estimate the dose of the drug that provides a therapeutic effect while minimizing the side effects of therapy.
