Lung adenocarcinoma‐related TNF‐α‐dependent inflammation upregulates MHC‐II on alveolar type II cells through CXCR‐2 to contribute to Treg expansion

Guo, Ningfei; Yang, Wen; Wang, Can; Kang, Lifei; Wang, Xiuqing; Liu, Xiaoyi; Soulika, Athena M.; Liu, Bowei; Zhao, Ming; Han, Xin; Lv, Ping; Xing, Lingxiao; Zhang, Xianghong; Shen, Haitao

doi:10.1096/fj.202000166rr

Cited by 10 publications

(30 citation statements)

References 63 publications

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“…Because AT-II cells' primary function is not antigen presentation, they lack co-stimulatory signals (CD80/CD86), essential to effectively prime CD4 + T cells. Thus, instead of creating an antitumor immune response, increased AT-II cell-specific MHC-II expression can trigger Treg differentiation [104]. Numerous studies evaluated TNFR2 as a potential biomarker for NSCLC as it has been shown to be crucial for TNFα-mediated immunosuppression [105,106].…”

Section: Specificities Of Tnfα In Lung Cancer Progressionmentioning

confidence: 99%

TNFα and Immune Checkpoint Inhibition: Friend or Foe for Lung Cancer?

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Piccioni

Ridder

et al. 2021

IJMS

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Tumor necrosis factor-alpha (TNFα) can bind two distinct receptors (TNFR1/2). The transmembrane form (tmTNFα) preferentially binds to TNFR2. Upon tmTNFα cleavage by the TNF-alpha-converting enzyme (TACE), its soluble (sTNFα) form is released with higher affinity for TNFR1. This assortment empowers TNFα with a plethora of opposing roles in the processes of tumor cell survival (and apoptosis) and anti-tumor immune stimulation (and suppression), in addition to angiogenesis and metastases. Its functions and biomarker potential to predict cancer progression and response to immunotherapy are reviewed here, with a focus on lung cancer. By mining existing sequencing data, we further demonstrate that the expression levels of TNF and TACE are significantly decreased in lung adenocarcinoma patients, while the TNFR1/TNFR2 balance are increased. We conclude that the biomarker potential of TNFα alone will most likely not provide conclusive findings, but that TACE could have a key role along with the delicate balance of sTNFα/tmTNFα as well as TNFR1/TNFR2, hence stressing the importance of more research into the potential of rationalized treatments that combine TNFα pathway modulators with immunotherapy for lung cancer patients.

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Section: Specificities Of Tnfα In Lung Cancer Progressionmentioning

confidence: 99%

TNFα and Immune Checkpoint Inhibition: Friend or Foe for Lung Cancer?

Benoot

Piccioni

Ridder

et al. 2021

IJMS

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“…The tissues or cells were harvested and homogenized in 50 μl lysis buffer (50 mM Tris–HCl pH 7.5, 150 mM NaCl, 2 mM EDTA, 1% TritonX‐100, cocktail). The protocol was according to our previous experiments 2,3 …”

Section: Methodsmentioning

confidence: 99%

“…28 TNF-α is an important regulator of the tumor inflammatory microenvironment, driving lung adenocarcinoma. [2][3][4] Our recent study showed that urethane induced inflammation-driven lung adenocarcinoma (IDLA) in mice, which is dependent on TNF-αinflammatory pathway. 2,3 Therefore, it is necessary to explore how lung inflammation depends TNF-α to reprogram macrophages upregulating PD-L1 at pro-tumor stage.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, using the urethane-induced IDLA mouse model as well as human lung adenocarcinoma samples, [2][3][4] we sought to investigate whether TNFα-mediated pro-tumor inflammation induces PD-L1 upregulation in macrophages to contribute to lung tumorigenesis. The effect of anti-PD-L1 treatment, at the pro-tumor inflammatory stage, on lung associated with enhanced T cells exhaustion in lung tissues.…”

Section: Introductionmentioning

confidence: 99%

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TNF‐α‐dependent lung inflammation upregulates PD‐L1 in monocyte‐derived macrophages to contribute to lung tumorigenesis

et al. 2022

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Chronic inflammation, which is dominated by macrophage-involved inflammatory responses, is an instigator of cancer initiation. Macrophages are the most abundant immune cells in healthy lungs, and associated with lung tumor development and promotion. PD-L1 is a negative molecule in macrophages and correlated with an immunosuppressive function in tumor environment. Macrophages expressing PD-L1, rather than tumor cells, exhibits a critical role in tumor growth and progression. However, whether and how PD-L1 in macrophages contributes to inflammationinduced lung tumorigenesis requires further elucidation. Here, we found that higher expression of PD-L1 in CD11b + CD206 + macrophages was positively correlated with tumor progression and PD-1 + CD8 + T cells population in human adenocarcinoma patients. In the urethane-induced inflammation-driven lung adenocarcinoma (IDLA) mouse model, the infiltration of circulating CD11b high F4/80 + monocyte-derived macrophages (MoMs) was increased in pro-tumor inflamed lung tissues and lung adenocarcinoma. PD-L1 was mainly upregulated in MoMsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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“…Macrophage receptor with collagenous structure (MARCO) expressed on the surface of tumor-associated macrophages (TAM) has been reported to promote the proliferation of Tregs and the inhibitory cytokine IL-10 secretion in NSCLC [68]. Besides, at the protumor inflammatory stage of lung cancer, TGF-α stimulation can upregulate MHC-II molecules on the surface of alveolar type II cells to trigger Treg expansion and promote the tumorigenesis of inflammation-driven lung adenocarcinoma [69].…”

Section: 3mentioning

confidence: 99%

Tumor-Associated Regulatory T Cells in Non-Small-Cell Lung Cancer: Current Advances and Future Perspectives

Liang

Shan

et al. 2022

Journal of Immunology Research

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Non-small-cell lung cancer (NSCLC) is one of the most threatening malignant tumors to human health, with the overall 5-year survival rate being less than 30%. Regulatory T cells (Tregs), a functional subset of T cells, maintain immunologic immunological self-tolerance and homeostasis. Accumulating evidence has uncovered their implicated roles in various cancers in recent years. In NSCLC, they are associated with staging, therapeutic efficacy, and prognosis by infiltrating in tissues and thereby attenuating immunologic anticancer effects in patients. Tumor-associated Tregs display distinct immune signatures in NSCLC compared to thymus-derived Tregs, playing an important role in remodeling the tumor microenvironment (TME). Targeting Tregs has become a novel direction for NSCLC patients, such as disrupting their immune-suppressive functions, blocking their trafficking into tumors, and inhibiting their development and/or activation. This review is aimed at elucidating the molecular mechanisms of tumor-associated Tregs in NSCLC and providing therapeutic targets relevant to Tregs.

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Lung adenocarcinoma‐related TNF‐α‐dependent inflammation upregulates MHC‐II on alveolar type II cells through CXCR‐2 to contribute to Treg expansion

Cited by 10 publications

References 63 publications

TNFα and Immune Checkpoint Inhibition: Friend or Foe for Lung Cancer?

TNFα and Immune Checkpoint Inhibition: Friend or Foe for Lung Cancer?

TNF‐α‐dependent lung inflammation upregulates PD‐L1 in monocyte‐derived macrophages to contribute to lung tumorigenesis

Tumor-Associated Regulatory T Cells in Non-Small-Cell Lung Cancer: Current Advances and Future Perspectives

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