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Xiaoxia Zhu
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P14 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Immuno-Biology (ID 153)
- Event: WCLC 2020
- Type: Posters
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P14.22 - Radiotherapy With Sequential αnti-PD-1 mAb Is Better in Enhancing the Abscopal Effect by Promoting the Inflammatory Tumor Microenvironment (ID 705)
00:00 - 00:00 | Presenting Author(s): Xiaoxia Zhu
- Abstract
Introduction
Radiotherapy (RT) is one of the main approaches for treatment of lung cancer. A large number of preclinical and several clinical studies revealed that RT can activate the host’s anti-tumor immune system and induce abscopal effect. However, the optimal timing and its underlying mechanism of the combination of RT and immune checkpoint inhibitor (CHI) are unclear.
Methods
MC38 cells were used for subcutaneous tumor formation in the left lower limbs (irradiation field) and the right lower limbs (non-irradiation field) of six-eight weeks old male C57BL/6 mice. When the tumor volume reached 150mm3, the mice were randomly assigned to receive RT (8Gy × 3F) with concurrent anti-PD-1 monoclonal antibody (mAb) or RT with sequential (1 week after the first irradiation) anti-PD-1 mAb (group B). The changes of immune microenvironment in irradiated and non-irradiated tumors in the two groups were analyzed by flow cytometry.
Results
Both RT with concurrent anti-PD-1 mAb and RT with sequential anti-PD-1 mAb could inhibit the growth of tumors in non-irradiation field. The number of CD4+T cells (CD45+CD44+CD4+T) and effector CD4+T cells (CD44+CD4+IFNγ + T) in non-irradiated tumors in the sequential group was significantly higher than that in the concurrent group, but which showed no significant difference between the two groups in irradiated tumors. Interestingly, CD8+T cells (CD45+CD44+CD8+T) and effector CD8+T cells (CD44+CD8+IFNγ + T) increased both in the irradiation and non-irradiation field in the sequential group compared with that in the concurrent group, while tumor associated macrophages (TAM, F4/80+CD11b+) and Treg cells (CD4+FoxP3+) in the sequential group decreased significantly. RT with sequential anti-PD-1 mAb reduced more exhausted CD8+T cells (PD-1+Eomes+of CD8+T) and induced more reinvigoration of exhausted T cell (Ki-67+PD-1+Emoes+CD8+T). The decrease of MDSCs (Gr1+CD11b+) in the non-irradiated tumors was observed in both groups, but there was no difference in the extent of this decrease between two groups.
Conclusion
Compared with the concurrent combination, RT with sequential anti-PD-1 mAb is more effective in promoting the inflammatory tumor microenvironment in out-field tumors and inducing the abscopal effect, which provides a new perspective for further exploring the mechanism of optimal timing of combination. Funding: 81972853, 81572279, 2016J004, LC2019ZD009, 2018CR033.
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P16 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Novel Immunotherapeutics (Translational) (ID 155)
- Event: WCLC 2020
- Type: Posters
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P16.01 - The Effect of Different Dose and Sites of Irradiation on Lymphocyte Subsets in Peripheral Blood of Patients With Lung Cancer (ID 710)
00:00 - 00:00 | Presenting Author(s): Xiaoxia Zhu
- Abstract
Introduction
To explore the effect of different irradiation doses and sites on systemic immunity in patients with lung cancer by detecting the changes in the percentage of lymphocyte subsets in peripheral blood before and after radiotherapy.
Methods
Peripheral blood in 48 patients with lung cancer receiving radiotherapy were collected (before, during and after radiation), and the lymphocyte subsets as follow were examined: total T cell (CD3+) , CD4+T cell , CD8+T cell , CD3+CD4+/CD3+CD8+, natural killer cell, memory T-helper cell subpopulation (CD4+ CD45RO+), CD4+ naïve T-cell subset (CD4+CD45RA+), cytotoxic T cell (CTL) (CD8+CD28+), interleukin-2 (IL-2) receptor α(CD25+), B cells (CD3-CD19+) , regulatory T cells (CD4+CD25+). The results were statistically analyzed with unpaired Student's t-test using GraphPrism6 software.
Results
Among non-small cell lung cancer (NSCLC) patients treated with thoracic radiation (n = 21), B cells in patients receiving 20Gy/10F (P = 0.0072), 40Gy/ 20F (P = 0.0001), 60Gy/30F (P = 0.0002) irradiation were significantly lower than that before radiotherapy. However, CD4+ naïve T-cells decreased significantly at each dose point compared with that before radiotherapy, P values were 0.0394, 0.0081 and 0.0007, respectively. NK cells after completion of 60Gy/30F irradiation were distinctly lower than those after receiving 20Gy/10F of radiotherapy (P = 0.0278), and no significant difference was found in other immune cell subsets. Patients with small cell lung cancer (n=6) who underwent thoracic radiation showed a similar trend of changes in B cells. However, the CD4+CD45RA+ subset decreased evidently after completing radiation compared with that after 10 fractions of irradiation (P=0.0390). The NSCLC patients (n=4) who received irradiation for bone metastases (regimen: 36Gy/12F) had evidently lower B cells (CD3-CD19+) at the end of radiotherapy than that at the start of radiotherapy (P=0.0286). Patients with NSCLC (n=10) who received brain radiation (regimen: 40Gy/20F for whole brain, 54-56Gy/20F for multiple brain metastases) had a significantly reduced CD4+CD45RA+ subsets after finishing irradiation (20F) compared with those after 10 fraction of radiotherapy (P= 0.0497). The changes of other subsets were not statistically significant.
Conclusion
The effect of radiation in different sites and doses on peripheral blood lymphocyte subsets is not identical.It is necessary to further expand the sample size to explore the law for the optimization of radiotherapy combined with immunotherapy.Funding: 81972853, 81572279, 2016J004, LC2019ZD009, 2018CR033.
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P19 - Locoregional and Oligometastatic Disease - Oligometastatic Disease (ID 129)
- Event: WCLC 2020
- Type: Posters
- Track: Locoregional and Oligometastatic Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P19.08 - Clinical Outcome of Local Treatment in Synchronous Oligometastatic Non-Small Cell Lung Cancer: A Preliminary Analysis of Prospective Data (ID 699)
00:00 - 00:00 | Presenting Author(s): Xiaoxia Zhu
- Abstract
Introduction
Advanced non-small cell lung cancer (NSCLC) is a heterogeneous disease, a large number of retrospective studies suggested that patients with oligometastases may achieve long-term survival from aggressive local treatment. However, relevant prospective studies were limited. Therefore, we prospectively evaluated the role of local treatment in synchronous oligometastatic NSCLC.
Methods
We prospectively identified 50 NSCLC patients newly diagnosed with synchronous oligometastases (≤5)in two centers between 11/2017 and 12/2019, among whom there were 24 patients from a randomized clinical trial NCT03119519. Patients were given first-line systemic therapy according to the latest NCCN guidelines with either local radiotherapy or surgery to thoracic primary tumor and/or radiotherapy to metastases. They were divided into combined therapies (Tx), systemic Tx and untreated groups. Kaplan Meier Survival analysis was used to compare progression free survival (PFS) and overall survival (OS) among the groups.
Results
Median age of all patients was 61 years old (range: 27-80 years) and median follow up was 5.7 months (range: 0.5-23.3 months). A total of 10 deaths were observed. In the combined Tx group, 23 patients received radiotherapy, and 2 patients received primary surgical resection. The median OS of the combined Tx group (n = 25), the systemic Tx group (n = 19) and the untreated group (n = 6) was 18.47 months, not reached, 3.27 months, respectively. Compared with the untreated group, the combined group and the systemic Tx group had better OS (hazard ratio [HR] = 0.1047, p = 0.0001; HR = 0.1125, p= 0.0006). However, the patients in the combined group did not show significant OS advantage compared with those in the systemic Tx group (HR = 1.376, p= 0.667). In addition, we conducted an ITT analysis in clinical trial NCT03119519, in which 8 progression events were observed. There was no significant difference in PFS between the combined group (n = 13) and the systemic Tx group (n = 11) (13.2 months vs. not reached, HR = 1.317, p= 0.7015; 1-year PFS: 74% vs. 54%, p=0.7015，respectively).
Conclusion
Current analysis shows that the addition of local treatment to first-line systemic Tx does not improve PFS and OS. More samples, further updated data and selection of potential beneficer are necessary. Funding: 81972853, 81572279, 2016J004, LC2019ZD009, 2018CR033.
