Message in a bottle from the tumor microenvironment: tumor-educated DCs instruct B cells to participate in immunosuppression

Mion, Francesca; Tonon, Silvia; Valeri, Viviana; Pucillo, Carlo

doi:10.1038/cmi.2017.63

Cited by 7 publications

(6 citation statements)

References 15 publications

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“…Therefore, multiple strategies such as DC vaccines, oncolytic viruses, and radiotherapy have been explored to modulate the TME with the goal of enhancing the anti-tumor effect. 31–35 For example, radiation-damaged tumor cells not only undergo a so-called immunogenic death that effectively exposes tumor antigens and triggers an antitumor immune response but also activate APCs through the release of damage-associated molecular pattern molecules (DAMPs). 36 Radiation therapy has the potential to trigger antigen-specific, adaptive immunity, a phenomenon called “in situ” vaccination, which improves the efficiency and survival rate combining with PD-1 blockade or another immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

Wang

et al. 2018

Cell Mol Immunol

113

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PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability. However, the therapeutic efficacy for patients with tumors with low microsatellite instability or stable microsatellites needs further improvement. Here, we have demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice. A more significant inhibition of tumor growth and a prolongation of survival were observed in the CT26 mouse model after treatment with a combination of PD-1 blockade and decitabine than in mice treated with decitabine or PD-1 blockade alone. The anti-tumor effect of the PD-1 blockade was enhanced by low-dose decitabine. The results of RNA sequencing and whole-genome bisulfite sequencing of decitabine-treated CT26 cells and tumor samples with microsatellite stability from the patient tumor-derived xenograft model have shown that many immune-related genes, including antigen-processing and antigen-presenting genes, were upregulated, whereas the promoter demethylation was downregulated after decitabine exposure. Therefore, decitabine-based tumor microenvironment re-modulation could improve the effect of the PD-1 blockade. The application of decitabine in PD-1 blockade-based immunotherapy may elicit more potent immune responses, which can provide clinical benefits to the colorectal cancer patients with low microsatellite instability or stable microsatellites.

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Section: Discussionmentioning

confidence: 99%

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

Wang

et al. 2018

Cell Mol Immunol

113

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“…52 The polarization of B cells to high IL-10-secreting cells is associated with high expression of inflammatory signals either derived from the tumor directly or indirectly by other microenvironment constituents. [53][54][55][56] In one model, LPS-stimulated lung cancer cells alone could polarize B cells to a Breg phenotype. Polarization was attributed to high secretion of RANTES, MIP-α, TNF-α, and TGF-β; thus, at least some differentiation factors could be directly attributed to epithelial tumor cells.…”

Section: Inhibitory Effect Of Bregs On Antitumor Immunity In Lung Cancermentioning

confidence: 99%

Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer

et al. 2018

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Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells, stromal fibroblasts, and immune cells. Tumor-infiltrating immune cells play a significant role in the promotion or inhibition of tumor growth. As an integral component of the tumor microenvironment, tumor-infiltrating B lymphocytes (TIBs) exist in all stages of cancer and play important roles in shaping tumor development. Here, we review recent clinical and preclinical studies that outline the role of TIBs in lung cancer development, assess their prognostic significance, and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment.

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“…The immunoregulatory functions of Breg cells have been investigated in different cancer models, shifting our understanding of how Breg function is regulated during tumor progression has become frontier of cancer immunotherapy. Moreover, analysis of the expression of several immunosuppressive membrane-bound molecules (such as CD80, CD86, PDL1, PD1, Fas-L, CD40L and OX40L) and secretion of various cytokines (such as IL-10, TGF-β and IL-35) by Bregs in specific tumor settings and stages of cancer has revealed functional complexity among the subsets of tumor-evoked Bregs [20].…”

Section: Role Of Regulatory B Cells (Bregs) In Ovarian Cancermentioning

confidence: 99%

B Cells as an Immune-Regulatory Signature in Ovarian Cancer

Gupta

Chen

Chaluvally‐Raghavan

et al. 2019

Cancers

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Increasing evidence suggests that the immune system plays a dynamic role in the progression of ovarian cancer, the deadliest gynecological malignancy worldwide. Accumulation of tumor-infiltrating lymphocytes has been associated with increased survival in ovarian cancer patients, and diverse interactions among immune cells in the tumor microenvironment determine tumor progression. While the regulatory functions of T cells among tumor-infiltrating lymphocytes are well defined and also involve therapeutic interventions, the role of B cells in ovarian cancer progression is still limited to their impact on survival. Recent studies have identified both pro- and anti-tumor responses of B cells in solid tumors, as different subsets of B cells play diverse roles in progression. Thus, in-depth characterization of B cell subtypes in each disease stage is crucial for understanding the importance and therapeutic potential of these cells in ovarian cancer. In this review, we summarize current knowledge about B cells in ovarian cancer and discuss emerging therapeutic interventions that could harness B cells to combat this deadly disease.

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Message in a bottle from the tumor microenvironment: tumor-educated DCs instruct B cells to participate in immunosuppression

Cited by 7 publications

References 15 publications

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer

B Cells as an Immune-Regulatory Signature in Ovarian Cancer

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