RETRACTED: Aberrant frequency of IL-10-producing B cells and its association with Treg and MDSC cells in Non Small Cell Lung Carcinoma patients

Liu, Jinlin; Wang, Huan; Yu, Qinhua; Zheng, Sujie; Jiang, Yangcheng; Liu, Yiyan; Yuan, Guandou; Qiu, Liannv

doi:10.1016/j.humimm.2015.10.015

Cited by 45 publications

(35 citation statements)

References 20 publications

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“…9a, b, and d). To our knowledge, the only other studies examining relationships of MDSCs and Bregs were correlative studies from human samples (121), which showed that numbers of IL-10-producing Bregs correlated with MDSC numbers, and a study in a murine lupus model, in which injection of MDSCs increased the number of IL-10 producing Bregs (38), making the direct ex vivo suppression (rather than enhancement) of Breg cells by M-MDSCs observed here a novel finding, and indicating that the effect of MDSC on Bregs, whether it be enhancement or suppression, may be dependent on the system. LP-BM5-expanded M-MDSCs were capable of decreasing the frequency of both IL-10-producing Tregs (22) and Bregs (Fig.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β

Rastad

Green

2016

Virology

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Monocytic myeloid-derived suppressor cells (M-MDSCs) were increased during LP-BM5 retroviral infection, and were capable of suppressing not only T-cell, but also B-cell responses. In addition to previously demonstrating iNOS- and VISTA-dependent M-MDSC mechanisms, in this paper, we detail how M-MDSCs utilized soluble mediators, including the reactive oxygen and nitrogen species superoxide, peroxynitrite, and nitric oxide, and TGF-β, to suppress B cells in a predominantly contact-independent manner. Suppression was independent of cysteine-depletion and hydrogen peroxide production. When two major mechanisms of suppression (iNOS and VISTA) were eliminated in double knockout mice, M-MDSCs from LP-BM5-infected mice were able to compensate using other, soluble mechanisms in order to maintain suppression of B cells. The IL-10 producing regulatory B-cell compartment was among the targets of M-MDSC-mediated suppression.

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Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β

Rastad

Green

2016

Virology

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“…The most prevalent TIL-B–mediated immunosuppression is secretion of IL10 by regulatory B cells (Bregs) (35–39). In NSCLC patients, the frequency and absolute number of IL10-producing Bregs is elevated and positively associated with advanced clinical stage (37). Further, Bregs can secrete IL35 and TGFβ, which can also suppress the immune response (40–42).…”

Section: Introductionmentioning

confidence: 99%

Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non–Small Cell Lung Cancer Patients

Bruno

Ebner

Moore

et al. 2017

Cancer Immunology Research

207

142

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Effective immunotherapy options for patients with non-small cell lung cancer (NSCLC) are becoming increasingly available. The immunotherapy focus has been on tumor infiltrating T cells (TILs); however, tumor infiltrating B cells (TIL-Bs) have also been reported to correlate with NSCLC patient survival. The function of TIL-Bs in human cancer has been understudied, with little focus on their role as antigen-presenting cells and their influence on CD4+ TILs. Compared to other immune subsets detected in freshly isolated primary tumors from NSCLC patients, we observed increased numbers of intratumoral B cells relative to B cells from tumor-adjacent tissues. Furthermore, we demonstrated that TIL-Bs can efficiently present antigen to CD4+ TILs and alter the CD4+ TIL phenotype using an in vitro antigen-presentation assay. Specifically, we identified three CD4+ TIL responses to TIL-Bs, which we categorized as: activated, antigen-associated, and non-responsive. Within the activated and antigen-associated CD4+ TIL population, activated TIL-Bs (CD19+CD20+CD69+CD27+CD21+) were associated with an effector T-cell response (IFNγ+ CD4+ TILs). Alternatively, exhausted TIL-Bs (CD19+CD20+CD69+CD27–CD21–) were associated with a regulatory T-cell phenotype (FoxP3+ CD4+ TILs). Our results demonstrate a new role for TIL-Bs in NSCLC tumors in their interplay with CD4+ TILs in the tumor microenvironment, establishing them as a potential therapeutic target in NSCLC immunotherapy.

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“…Response to checkpoint blockade is also likely affected by cytotoxic T lymphocyte-extrinsic (CTL-extrinsic) factors as well, such as the presence of myeloid-derived suppressor cells (MDSCs) and FOXP3 + Tregs, the latter of which have been documented in NSCLC (12). The presence of MDSCs and Tregs in NSCLC is positively correlated with an abundance of IL-10-producing B regulatory cells (Bregs); all three are associated with NSCLC progression (13).…”

Section: Introductionmentioning

confidence: 99%

Multiparametric profiling of non–small-cell lung cancers reveals distinct immunophenotypes

Lizotte¹,

Ivanova²,

et al. 2016

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BACKGROUND.Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS.We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). RESULTS.Cytometric profiling identified an immunologically "hot" cluster with abundant CD8 + T cells expressing high levels of PD-1 and TIM-3 and an immunologically "cold" cluster with lower relative abundance of CD8 + T cells and expression of inhibitory markers. The "hot" cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the "hot" cluster. Additionally, approximately 20% of cases had high B cell infiltrates with a subset producing IL-10. CONCLUSIONS.Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer.

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RETRACTED: Aberrant frequency of IL-10-producing B cells and its association with Treg and MDSC cells in Non Small Cell Lung Carcinoma patients

Cited by 45 publications

References 20 publications

Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β

Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β

Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non–Small Cell Lung Cancer Patients

Multiparametric profiling of non–small-cell lung cancers reveals distinct immunophenotypes

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