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MDSC subtypes and CD39 expression on CD8⁺ T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC.

ABSTRACT: The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T-cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non-small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T-cell activities leading to poor clinical outcomes. First, we verified PMN-MDSCs, monocytic-MDSCs (M-MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T-cell activities and induced T-cell exhaustion. The analysis of NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that low PMN-MDSCs, M-MDSCs, and CD39⁺ CD8⁺ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN-MDSCs, M-MDSCs, and CD39⁺ CD8⁺ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.

SUBMITTER: Koh J

PROVIDER: S-EPMC7689686 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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MDSC subtypes and CD39 expression on CD8<sup>+</sup> T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC.

Koh Jiae J Kim Youjin Y Lee Kyoung Young KY Hur Joon Young JY Kim Mi Soon MS Kim Boram B Cho Hee Jin HJ Lee Yeong Chan YC Bae Yeon Hee YH Ku Bo Mi BM Sun Jong-Mu JM Lee Se-Hoon SH Ahn Jin Seok JS Park Keunchil K Ahn Myung-Ju MJ

European journal of immunology 20200709 11

The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T-cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non-small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T-cell activities leading to poor clinical outco ...[more]

PMID: 32510574

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Project description:IntroductionImmunotherapy has improved outcomes for patients with non-small cell lung cancer (NSCLC), yet durable clinical benefit (DCB) is experienced in only a fraction of patients. Here, we test the hypothesis that radiomics features from baseline pretreatment 18F-FDG PET/CT scans can predict clinical outcomes of NSCLC patients treated with checkpoint blockade immunotherapy.MethodsThis study included 194 patients with histologically confirmed stage IIIB-IV NSCLC with pretreatment PET/CT images. Radiomics features were extracted from PET, CT, and PET+CT fusion images based on minimum Kullback-Leibler divergence (KLD) criteria. The radiomics features from 99 retrospective patients were used to train a multiparametric radiomics signature (mpRS) to predict DCB using an improved least absolute shrinkage and selection operator (LASSO) method, which was subsequently validated in both retrospective (N = 47) and prospective test cohorts (N = 48). Using these cohorts, the mpRS was also used to predict progression-free survival (PFS) and overall survival (OS) by training nomogram models using multivariable Cox regression analyses with additional clinical characteristics incorporated.ResultsThe mpRS could predict patients who will receive DCB, with areas under receiver operating characteristic curves (AUCs) of 0.86 (95%CI 0.79-0.94), 0.83 (95%CI 0.71-0.94), and 0.81 (95%CI 0.68-0.92) in the training, retrospective test, and prospective test cohorts, respectively. In the same three cohorts, respectively, nomogram models achieved C-indices of 0.74 (95%CI 0.68-0.80), 0.74 (95%CI 0.66-0.82), and 0.77 (95%CI 0.69-0.84) to predict PFS and C-indices of 0.83 (95%CI 0.77-0.88), 0.83 (95%CI 0.71-0.94), and 0.80 (95%CI 0.69-0.91) to predict OS.ConclusionPET/CT-based signature can be used prior to initiation of immunotherapy to identify NSCLC patients most likely to benefit from immunotherapy. As such, these data may be leveraged to improve more precise and individualized decision support in the treatment of patients with advanced NSCLC.

Dataset Information

MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC.

Publications

MDSC subtypes and CD39 expression on CD8<sup>+</sup> T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC.

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MDSC subtypes and CD39 expression on CD8⁺ T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC.