Dataset Information

The prognostic role of circulating CD8⁺ T cell proliferation in patients with untreated extensive stage small cell lung cancer.

ABSTRACT:

Background

Immunosuppression caused by tumorigenesis may promote tumor progress and invasion. Here, we investigated whether the characteristics of circulating T lymphocyte subtypes in patients with extensive small cell lung cancer (ED-SCLC) can be used as an alternative marker of tumor progression.

Methods

This study included 36 newly diagnosed ED-SCLC patients before treatment and the patients were followed up. 22 age and sex-matched healthy volunteers were selected as control. The percentages and proliferation potential of T lymphocyte subpopulations from peripheral blood were measured.

Results

CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells (Tregs) were elevated in ED-SCLC patients compared with healthy controls (p?=?0.0083). In contrast, the percentages of CD3⁺ and CD3⁺CD4⁺ T cells were significantly lower in SCLC patients (p?+ T cells of SCLC patients was suppressed compared with healthy controls (p?=?0.0058), but not of CD4⁺ T cells (p?=?0.1611). Multivariate analyses showed that the %divided of CD8⁺ T cells is an independent predictor for PFS (HR: 4.342, 95% CI 1.324-14.245; p?=?0.015). The percentages of peripheral Tregs and the degree of chemotherapy or radiotherapy induced lymphopenia negatively correlated with the proliferation of CD8⁺ T cells (p?=?0.0225, r?=?-?0.379; p?=?0.0003, r?=?-?0.464).

Conclusion

The present study indicates that SCLC patients have impaired immunity in peripheral blood, and the proliferation potential of circulating CD8⁺ T cells is a significant predicator for PFS.

SUBMITTER: An N

PROVIDER: S-EPMC6892179 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

The prognostic role of circulating CD8<sup>+</sup> T cell proliferation in patients with untreated extensive stage small cell lung cancer.

An Ning N Wang Haoyi H Jia Wenxiao W Jing Wang W Liu Chao C Zhu Hui H Yu Jinming J

Journal of translational medicine 20191203 1

<h4>Background</h4>Immunosuppression caused by tumorigenesis may promote tumor progress and invasion. Here, we investigated whether the characteristics of circulating T lymphocyte subtypes in patients with extensive small cell lung cancer (ED-SCLC) can be used as an alternative marker of tumor progression.<h4>Methods</h4>This study included 36 newly diagnosed ED-SCLC patients before treatment and the patients were followed up. 22 age and sex-matched healthy volunteers were selected as control. T ...[more]

PMID: 31796037

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Project description:Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) therapy (chemo-immunotherapy). We previously observed that the increase of peripheral blood CD8+ T cells expressing CX3CR1, a marker of differentiation, correlates with response to anti-PD-1 therapy; however, the predictive and prognostic value of T-cell CX3CR1 expression during chemo-immunotherapy is unknown. Here, we evaluated the utility of circulating CX3CR1+CD8+ T cells as a predictive correlate of response to chemo-immunotherapy in patients with non-small cell lung cancer (NSCLC). At least 10% increase of the CX3CR1+ subset in circulating CD8+ T cells from baseline (CX3CR1 score) was associated with response to chemo-immunotherapy as early as 4 weeks with 85.7% overall accuracy of predicting response at 6 weeks. Furthermore, at least 10% increase of the CX3CR1 score correlated with substantially better progression-free (P = 0.0051) and overall survival (P = 0.0138) on Kaplan-Meier analysis. Combined single-cell RNA/T-cell receptor (TCR) sequencing of circulating T cells from longitudinally obtained blood samples and TCR sequencing of tumor tissue from the same patient who received a long-term benefit from the treatment demonstrated remarkable changes in genomic and transcriptomic signatures of T cells as well as evolution of TCR clonotypes in peripheral blood containing highly frequent tumor-infiltrating lymphocyte repertoires overexpressing CX3CR1 early after initiation of the treatment despite stable findings of the imaging study. Collectively, these findings highlight the potential utility of T-cell CX3CR1 expression as a dynamic blood-based biomarker during the early course of chemo-immunotherapy and a marker to identify frequent circulating tumor-infiltrating lymphocyte repertoires.SignificanceCurrent approaches to combined chemotherapy and anti-PD-1/PD-L1 therapy (chemo-immunotherapy) for patients with NSCLC are limited by the lack of reliable predictive biomarkers. This study shows the utility of T-cell differentiation marker, CX3CR1, as an early on-treatment predictor of response and changes in genomic/transcriptomic signatures of circulating tumor-infiltrating lymphocyte repertoires in patients with NSCLC undergoing chemo-immunotherapy.

Dataset Information

The prognostic role of circulating CD8⁺ T cell proliferation in patients with untreated extensive stage small cell lung cancer.

Background

Methods

Results

Conclusion

Publications

The prognostic role of circulating CD8<sup>+</sup> T cell proliferation in patients with untreated extensive stage small cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

The prognostic role of circulating CD8+ T cell proliferation in patients with untreated extensive stage small cell lung cancer.

Background

Methods

Results

Conclusion

Publications

The prognostic role of circulating CD8<sup>+</sup> T cell proliferation in patients with untreated extensive stage small cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The prognostic role of circulating CD8⁺ T cell proliferation in patients with untreated extensive stage small cell lung cancer.