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Jiae Koh
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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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P14.25 - Immune Cell Profiling of Hyperprogressive Disease in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1/PD-L1 Antibodies (ID 3272)
00:00 - 00:00 | Author(s): Jiae Koh
- Abstract
Introduction
Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 antibodies. However, the immunological characteristics have not been fully elucidated in patients with HPD. In the present study, we aimed to uncover the immunological characteristics specific to HPD using peripheral blood obtained before and early after anti-PD-1/PD-L1 treatment in patients with non-small cell lung cancer (NSCLC).
Methods
We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 antibodies between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥ 2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment. From peripheral blood mononuclear cells, CD8+ and CD4+ T cells, regulatory T cells, and myeloid derived suppressor cells were analyzed by multi-color flow cytometry.
Results
Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (P < 0.001) and overall survival (P < 0.001). A total of 72 immune cell parameters were analyzed and the pre-treatment frequency of CD39+ cells among CD8+ T cells was significantly higher in patients with HPD compared to those with NHPD. Other parameters regarding the proliferative response or frequency of total regulatory T cells, effector regulatory T cells (FoxP3hiCD45RA-) or myeloid derived suppressor cells did not significantly differ among DCB, NHPD, and HPD groups.
Conclusion
Our findings suggest high pre-treatment frequency of CD39+CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.
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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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P60.09 - High Circulating Regulatory (FoxP3+) T Cells and TGF-β Predict the Response to Anti-PD-1 Immunotherapy in NSCLC Patients (ID 3270)
00:00 - 00:00 | Presenting Author(s): Jiae Koh
- Abstract
Introduction
Antitumor immune response induced by immune checkpoint inhibitors including anti-PD-1 or anti-PD-L1 in advanced non-small cell lung cancer (NSCLC) patients has been shown as promising new therapeutic strategies for the last decade. It has been reported that favorable antitumor activities to immune checkpoint inhibitor are strongly correlated with high PD-L1 expression, increased tumor infiltrating lymphocytes, and decreased suppressive immune cells including Treg cells, myeloid-derived suppressor cells (MDSCs), or tumor associated macrophages (TAMs) in various cancer types. The accumulation of Treg cells in tumor bed among various cancers is known to be associated with poor prognosis, as expected from their function inhibiting antitumor immunity and maintaining immune homeostasis. However, Treg cells frequencies in several cancer types showed the opposite results; a high Treg cell infiltration is associated with a favorable prognosis in patients bearing colorectal cancer, or ER- breast cancer.
Methods
The patients with NSCLC (stage IIIB to IV) undergoing anti-PD-1 immunotherapy with either pembrolizumab (200 mg every 3 weeks) or nivolumab (2 mg/kg every 2 weeks) were enrolled in a part of a phase II clinical trial (NCT02607631) at Samsung Medical Center (Korea). Baseline and one week after anti-PD-1 therapy peripheral blood samples were collected from March 2017 to February 2018 for discovery cohort (n = 83), and March 2018 to March 2019 for validation cohort (n = 49). Treg cells, PMN-MDSCs, M-MDSCs were analyzed their correlation with clinical outcomes including PFS (progression free survival) and OS (overall survival). mRNA and plasma level of TGF-β were also measured and analyzed the correlation with Treg cells and clinical outcomes.
Results
Treg cell frequencies high group showed longer PFS and OS and especially, high Treg cell frequency one week after anti-PD-1 therapy showed more distinct differences compared with Treg cells low group of the patients. Treg cells high frequency group was associated with relatively low PMN-MDSCs frequencies, and combined analysis of Treg cells high and PMN-MDSCs or M-MDSC low group showed better OS compared with Treg cells low and PMN-MDSC or M-MDSC high group. TGF-β mRNA expression correlated with Treg cells and clinical outcomes. Various cytokines in plasma correlated with Treg cells and clinical outcomes.
Conclusion
Our results suggest the favorable prognostic value of high circulating CD4+CD25+CD45RA-FoxP3+ T cells (effector Treg cells) frequencies one week after the immunotherapy in NSCLC patients who were treated with anti-PD-1 immunotherapy, either pembrolizumab or nivolumab. Together with Treg cells, the detection of a high TGF-β also identifies a more favorable outcome which may specifically benefit from anti-PD-1 immunotherapy. The understanding of the clinical relevance of the tumor microenvironmental immunologic milieu might provide an important clue when designing novel strategies in cancer immunotherapy, however, blood based Treg cells might also provide alternative sources when tumor biopsy is not available. Therefore, Treg cells frequencies and TGF-β expression level might be used as blood-based biomarkers to predict the response of anti-PD-1 immunotherapy in advanced NSCLC patients.
