Low-Dose IFNγ Induces Tumor Cell Stemness in Tumor Microenvironment of Non–Small Cell Lung Cancer

Song, Mengjia; Yü, Ping; Zhang, Kai; Li, Yang; Li, Feng; Zhang, Chaoqi; Cheng, Shaoyan; Yue, Dongli; Maimela, Nomathamsanqa Resegofetse; Qu, Jiao; Li, Shasha; Sun, Ting; Li, Zihai; Xia, Jianchuan; Zhang, Bin; Wang, Liping; Zhang, Yi

doi:10.1158/0008-5472.can-19-0596

Cited by 112 publications

(95 citation statements)

References 43 publications

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“…The underlying mechanism of IFN-induced CSC properties may be dependent, at least in part, on its concentration. Thus, IFNγ at low concentrations induced CSC properties in non-small cell lung cancer through the ICAM1/PI3K/AKT/NOTCH1 pathway, whereas it induced apoptosis through the JAK1/STAT1/caspase pathway at high concentrations [ 172 ].…”

Section: Immunosuppressive Properties Endowed On Cscsmentioning

confidence: 99%

Immune evasion by cancer stem cells

Tsuchiya

Shiota

2021

Regenerative Therapy

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Tumor immunity represents a new avenue for cancer therapy. Immune checkpoint inhibitors have successfully improved outcomes in several tumor types. In addition, currently, immune cell-based therapy is also attracting significant attention. However, the clinical efficacy of these treatments requires further improvement. The mechanisms through which cancer cells escape the immune response must be identified and clarified. Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors. CSCs can initiate tumors in partially immunocompromised mice, whereas non-CSCs fail to form tumors, suggesting that tumor initiation is a definitive function of CSCs. However, the fact that non-CSCs also initiate tumors in more highly immunocompromised mice suggests that the immune evasion property may be a more fundamental feature of CSCs rather than a tumor-initiating property. In this review, we summarize studies that have elucidated how CSCs evade tumor immunity and create an immunosuppressive milieu with a focus on CSC-specific characteristics and functions. These profound mechanisms provide important clues for the development of novel tumor immunotherapies.

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Section: Immunosuppressive Properties Endowed On Cscsmentioning

confidence: 99%

Immune evasion by cancer stem cells

Tsuchiya

Shiota

2021

Regenerative Therapy

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“…The detection of whole cell lysates were carried out as described in previous report (Song et al, 2019). Briefly, 293T cells were fractured using lysis buffer containing RIPA (Beyotime, Cat.…”

Section: Western Blotmentioning

confidence: 99%

Augmenting the Effectiveness of CAR-T Cells by Enhanced Self-Delivery of PD-1-Neutralizing scFv

Yü

Nan

et al. 2020

Front. Cell Dev. Biol.

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Chimeric antigen receptor T (CAR-T) cell therapy is not satisfying in solid tumors. PD-1-mediated suppression greatly hinders CART cells in the microenvironment. It has been shown that PD-1 blockade improves the effectiveness of CART cells. Herein, we designed CART cells than could secret α-PD-1 scFv by themselves. To obtain optimal secretions of scFv, we screened several signal peptides. And the segment from human increased the extracellular production of PD-1-neutralizing proteins. The secreted neutralizing scFv efficiently blocked PD-1 and enhanced T cell activation when PD-L1 was present. Further analysis showed that CART cells themselves could secret α-PD-1 scFv with bioactivity. In contrast to the prototype, the scFv-producing CART cells demonstrated decreased PD-1 but increases expansion and toxicity against solid tumor cells. In the subcutaneous and orthotopic xenograft models, the self-delivered α-PD-1 scFv increased CART cell functionalities and tumor-suppressions. Our work suggested that engineering T cells to co-express antigen-responsive receptors and checkpoint inhibitors is effective to optimize CART cell therapy for solid tumors.

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“…Increased immunotherapy response is associated with the expression of CCL4 [ 44 ]. In the tumor microenvironment of non-small cell lung cancer, decreased IFNG is linked with the stemness of tumor cells [ 45 ]. Taken together, the expression level of ACE2 is inversely associated with the anti-tumor immunity in lung adenocarcinoma.…”

Section: Resultsmentioning

confidence: 99%