MON-315 Transcription Factor NRF2 May Serve as a Master Regulator of Immune Modulation and Lung Cancer Progression

Tumor-stromal interactions within the tumor microenvironment (TME) influence lung cancer progression and response to therapeutic interventions, yet traditional in vitro studies fail to replicate the complexity of these interactions. Herein, we developed three-dimensional (3D) lung tumor models that mimic the human TME and demonstrate tumor-stromal crosstalk mediated by extracellular vesicles (EVs). EVs released by tumor cells, independent of p53 status, and fibroblasts within the TME mediate immunomodulatory effects; specifically, monocyte/macrophage polarization to a tumor-promoting M2 phenotype within this 3D-TME. Additionally, immune checkpoint inhibition in a 3D model that included T cells showed an inhibition of tumor growth and reduced hypoxia within the TME. Thus, perfused 3D tumor models incorporating diverse cell types provide novel insights into EV-mediated tumor-immune interactions and immune-modulation for existing and emerging cancer therapies.

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Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients

Cell Reports ◽

10.1016/j.celrep.2016.06.020 ◽

2016 ◽

Vol 16 (3) ◽

pp. 631-643 ◽

Cited By ~ 63

Author(s):

Ekaterina A. Semenova ◽

Min-chul Kwon ◽

Kim Monkhorst ◽

Ji-Ying Song ◽

Rajith Bhaskaran ◽

...

Keyword(s):

Lung Cancer ◽

Transcription Factor ◽

Small Cell Lung Cancer ◽

Cancer Progression ◽

Metastatic Disease ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

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NFIX as a Master Regulator for Lung Cancer Progression

Frontiers in Pharmacology ◽

10.3389/fphar.2017.00540 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 6

Author(s):

Nor I. A. Rahman ◽

Nor A. Abdul Murad ◽

Mohammad M. Mollah ◽

Rahman Jamal ◽

Roslan Harun

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Master Regulator

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Recombinant protein rMBP-NAP restricts tumor progression by triggering antitumor immunity in mouse metastatic lung cancer

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0186 ◽

2018 ◽

Vol 96 (2) ◽

pp. 113-119 ◽

Cited By ~ 1

Author(s):

Ting Wang ◽

Mingxuan Du ◽

Zhenyu Ji ◽

Cong Ding ◽

Chengbo Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Immune Modulation ◽

Antitumor Immunity ◽

Lung Tumor ◽

Metastatic Lung Cancer ◽

Melanoma Metastases ◽

Metastatic Lung ◽

Tlr2 Ligand ◽

Local Immune Modulation

Recombinant Helicobacter pylori neutrophil-activating protein fused with maltose-binding protein (rMBP-NAP), a potential TLR2 ligand, was reported to possess immunomodulatory effects on in situ tumors in our previous study. In the present work, we attempt to elucidate the effect of rMBP-NAP at the local immune modulation in B16-F10-induced metastatic lung cancer. Our results demonstrated that growth of B16-F10 melanoma metastases in the lung was significantly arrested after rMBP-NAP treatment, along with marked reduction in metastatic lung nodules and significant increase in survival. The treatment induced both local and systemic immune responses, which were associated with higher influx of CD4+/CD8+ T cells and drove toward Th1-like and cytotoxic immune environment. Moreover, rMBP-NAP also showed significant anti-angiogenic activity by reducing vascularization in lung tumor sections. rMBP-NAP could induce antitumor immunity through activating Th1 cells and producing pro-inflammatory cytokines, which are responsible for the effective cytotoxic immune response against cancer progression. Our findings indicate that rMBP-NAP might be a novel antitumor therapeutic strategy.

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