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LIANGLIANG XU



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    P07 - Early Stage/Localized Disease - Imaging and Biomarkers (ID 116)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P07.08 - IDO Immune Suppression and Post Surgical Toxicity in Patients with Non-Small Cell Lung Cancer (ID 3835)

      00:00 - 00:00  |  Author(s): LIANGLIANG XU

      • Abstract
      • Slides

      Introduction

      A powerful blood biomarker could assist surgeon in determining the factors affecting the surgery toxicity of the lung cancer patients. Here, we evaluate the activity of the indoleamine 2, 3-dioxygenase (IDO) 1 , which was indicated by the ration of kyn and trp, in the blood and analyzed the association of the IDO1 activity with the post-surgery toxicity in patients with lung cancer. Hence, we aimed to investigate the IDO1 activity in different steps of surgery operation and its relationship with post-surgery toxicity in patients with lung cancer.

      Methods

      This is part of prospective cross-sectional study of treatment toxicity, quality of life and biomarker study. Patients aged 18-year old and above requiring Q were eligible. The post toxicity was evaluated by the treating physicians and graded according to NIH/NCI CTCAE v4.0. The variables of our interest included age, gender, Body mass index (can be calculated), weight/weight loss, KPS, comorbidity score, smoking history, tumor type, stage, size, histology. The high-performance chromatography (Waters) was used for assay of the IDO1 activity. Briefly, the Mobile phase A (2.5% acetonitrile in distilled water and mobile phase acetonitrile were delivered with Solvent pumps at the flow rate of 0.4 ml per minute (0 to 2.5 minutes 100% A, 2.5 to 4 minutes 100% A to 90% A linear gradient). Kynurenine was detected on an UV/vis channel at 360nm and tryptophan was detected at 285nm excitation. Data are presented as mean (95% confidence interval), OR (odds ratio) unless otherwise specified. Statistical significances were tested using the linear regression model. P < 0.05 were considered to be significant.

      Results

      A total of 105 patients scheduled to thoracic surgery enrolled this study. The blood samples of the patients were collected in five time-points: pre-anesthesia, post-anesthesia, before blood vessel cut, sample removal, 3 days of post-surgery. We found that the hiccups was closely associated with the IDO1 activity in blood taken before the step of blood vessel cut (OR = 1.34, CI: 1.15-1.58, p = 7E-04). Interesting, we also found that the hoarseness symptoms was closely associated with IDO1 activity in blood taken 3 days post-surgery (OR = 15.49, CI:2.09-114.89, p = 0.01). Furthermore, the constipation symptoms were associated with the blood taken when the samples were removed (OR = 1.349, CI:1.033-1.761, p = 0.03).

      Conclusion

      This study showed a close relationship between the IDO1 activity with the post surgery toxicity in patients with non-small cell lung cancer. Further validation study is warranted to validate our findings with large sample size of patients and further consideration of other confounding factors. This finding might reveal a potential role of IDO1 immune biomarker in defining approaches of surgery management to improve quality of life.

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    P33 - Pathology - Immunotherapy Biomarker (ID 101)

    • 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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      P33.03 - Alteration of Circulating Blood Lymphocyte Subtypes Reveal Therapy Effect in Non-small Cell Lung Cancer (ID 3182)

      00:00 - 00:00  |  Presenting Author(s): LIANGLIANG XU

      • Abstract
      • Slides

      Introduction

      Lung cancer is the leading mortality regarding cancer-related death worldwide. Radiotherapy (RT) and surgical resection (SR) as two main local therapies in NSCLC have either suppressive or stimulatory effects on the immune system. The abscopal effect induced by RT may be one of the positive consequences of immune regulation. It is widely reported that RT can reduce the circulating lymphocyte counts and tumor-infiltrating lymphocytes. Similarly, the rising numbers of circulating monocytes in the SR patients indicate the complicated immune regulation. It’s still unclear the mechanism involved in the systemic changes of immune cells in the blood. Peripheral blood lymphocyte subpopulations were useful markers for evaluating immune response in tumor patients. Hence, we aimed to systematically investigate the alteration of lymphocyte subpopulations during the local therapies to evaluate antitumor treatment effects.

      Methods

      Primary tumor patients treated with localized therapies were recruited to a prospective study for the peripheral blood collection. The following antibodies were used in the lymphocyte subtyping: CD11b, CD45, CD19, CD3, CD56, CD4, CD8a, and FOXP3. The staining cells were detected by flow cytometry and data were analyzed by the paired T-test. The percentage of Lymphocytes, Myeloid cells, B cells, T cells, Treg, CD8+ T cells, CD4+ T cells, NK cells, and NKT were examined. The baseline between RT and SR was analyzed by the unpaired T-test. P<0.05 was considered as statistical significance. We included RT and SR as they are the main local therapy to the patients with NSCLC.

      Results

      Between July 2019 and January 2020, a total of 119 patients eligible, including 57 RT patients and 29 SR patients with both blood collection with both Pre and End therapies.

      Before local therapies, the percentage of total T cells in the RT group was significantly higher than SR (RT v.s SR mean:64.1 v.s 55.3, P=0.02) while CD8+ T cells (RT v.s SR mean:28.2 v.s 34.5, P=0.04)and Tregs (RT v.s SR mean:0.0 v.s 0.1, P=0.055) were lower. The baseline level of T cells and their subtypes showed a significant difference in these two group patients. After local therapies, myeloid Cells, lymphocytes, CD4+ T cells, CD8+ T cells, NK cells were significantly different.

      In the RT group, lymphocytes (Pre-RT v.s End-RT mean:75.2 v.s 54.3, P=0.004) and B cells (Pre-RT v.s End-RT mean:12.6 v.s 8.0, P=0.03) were significantly decreased while other subpopulations didn’t show any significant difference after RT. Interestingly, in the SR group, there was a significant increase in CD4+ T cells (mean:59.0 v.s 62.1, p=0.02) a trend of reduction in CD8+ T cells (mean:34.5 v.s 32.0, p=0.055) after SR.

      Conclusion

      There are some different patterns of distribution in subtypes of leukocytes in operable and inoperable patients and between different local therapies. Both RT and SR changed the distribution of peripheral blood lymphocyte subpopulations. Further validation study is warranted to validate our findings particularly in circulating lymphocytes and B cells as a marker to evaluate immune status after RT, CD4+ T cells and CD8+ T cells after SR as well as their relationship with tumor microenvironment and implication for personalized care.

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