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Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma

ABSTRACT: Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma

PROVIDER: PRJNA683887 | ENA |

REPOSITORIES: ENA

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Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma [RNA-seq]

Project description:Background and purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens.

2020-12-10 | GSE162945 | GEO

Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma [exome-seq]

2020-12-10 | GSE162944 | GEO

Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma [exome-seq]

Project description:Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma [exome-seq]

| PRJNA683893 | ENA

Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma [RNA-seq]

| PRJNA683894 | ENA

Modulation of the human pancreatic ductal adenocarcinoma immune microenvironment by stereotactic body radiotherapy

Project description:Purpose: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC) that can effectively prime cytotoxic T cells by inducing immunogenic tumor cell death in preclinical models. SBRT effects on human PDAC have yet to be thoroughly investigated, therefore, this study aimed to characterize immunomodulation in the human PDAC tumor microenvironment following therapy. Experimental Design: Tumor samples were obtained from patients with resectable PDAC. Radiotherapy was delivered a median of seven days prior to surgical resection, and sections were analyzed by multiplex IHC (mIHC), RNA-Seq, and T cell receptor sequencing (TCR-Seq). Results: Analysis of SBRT-treated tumor tissue indicated reduced tumor cell density and increased immunogenic cell death relative to untreated controls. Radiotherapy promoted collagen deposition, however, vasculature was unaffected and spatial analyses lacked evidence of T cell sequestration. Conversely, SBRT resulted in fewer tertiary lymphoid structures and failed to lessen or reprogram abundant immune suppressor populations. Higher percentages of PD-1+ T cells were observed following SBRT, and a subset of tumors displayed more clonal T cell repertoires. Conclusions: These findings suggest that SBRT augmentation of antitumor immunogenicity may be dampened by an overabundance of refractory immunosuppressive populations, and support the continued development of SBRT/immunotherapy combination for human PDAC.

2021-10-08 | GSE185311 | GEO

Modulation of the human pancreatic ductal adenocarcinoma immune microenvironment by stereotactic body radiotherapy

Project description:Modulation of the human pancreatic ductal adenocarcinoma immune microenvironment by stereotactic body radiotherapy

| PRJNA768494 | ENA

Gene expression profiles of primary tumors with radiotherapy and lung metastases in mouse squamous cell carcinoma model.

2009-04-23 | GSE9305 | GEO

TGFÎ² confers resistance to radiotherapy in non-small cell lung cancer

Project description:Radiotherapy is standard of care for inoperable non-small cell lung cancers (NSCLC) but adenocarcinoma NSCLC respond more poorly than squamous cell NSCLC. Transforming growth factor Î² (TGFÎ²) activity is induced by radiation and plays a recently recognized role in the DNA damage response. Here we show in murine lung tumor model that radiation activates TGFÎ² acutely and persistently and that TGFÎ² neutralizing antibody, 1D11, systemic treatment increased tumor control following either fractionated or single high dose radiation regimes. TGFÎ² dependent genes in the irradiated tumor indicated crosstalk between innate and adaptive immunity but therapeutic benefit of 1D11 in irradiated tumors in immunocompromised mice suggested that innate immune cells are more influential than the adaptive immune response. Irradiated tumors in which TGFÎ² was blocked were highly hypoxic, exhibit pronounced microvascular damage and promoted neither cancer-associated fibroblasts nor recruit bone marrow derived cells (BMDC). Tumor educated immature BMDC were significant sources of TGFÎ² and inhibiting BMDC recruitment achieved tumor growth control in response to RT comparable to TGFÎ² inhibition. Thus, radiation-induced TGFÎ² both compromises tumor control by RT and promotes reestablishment of the tumor microenvironment. Concordant with the critical role of TGFÎ² activity in RT, radiation resistant NSCLC adenocarcinomas exhibit higher TGFÎ² activity compared to squamous cell NSCLC, which suggests a rationale for using TGFÎ² inhibition to augment radiotherapy. Lewis lung cancer (LLC) model were established in 6 to 8 week-old C57BL/6 female mice by subcutaneous injection. When tumors were 60-80 mm3, Mice were randomized to achieve comparable mean tumor size for each treatment group as indicated below. Tumor growth were monitored and tumors were collected and characterized by gene expression profiling and immunostaining.

2015-12-15 | E-GEOD-73095 | biostudies-arrayexpress

Gene expression profiles of primary tumors with radiotherapy and lung metastases in mouse squamous cell carcinoma model.

Project description:To examine whether the local carbon ion radiotherapy affects the characteristics of the metastatic tumors, the expression profiles of the primary tumors and the lung metastases were studied in a mouse squamous cell carcinoma model by applying local radiotherapy with no irradiation (negative control), gamma-ray irradiation (reference beam), and carbon-ion irradiation. Keywords: mouse, squamous cell carcinoma, primary tumor, lung metastases, radiotherapy, carbon ion, gamma ray A highly metastatic mouse squamous cell carcinoma NR-S1 was implanted into the hind leg of synergetic C3H/HeNrs mice and irradiated with 5 Gy of carbon ion beam. 8 Gy of gamma ray was used as a reference beam. At 2 weeks after the irradiation, the lung tissue was sampled. In order to collect samples of primary tumors, the tumors were implanted in other mice and irradiated in the same manner, and the primary tumors were collected at 1 week after the irradiation. The tumor cells of the primary and metastatic tumors were collected by laser microdissection, and oligonucleotide microarray analysis of the irradiated primary tumors and the metastatic tumors were all performed in comparison to the non-irradiated primary tumor by two-color methods.

2009-04-22 | E-GEOD-9305 | biostudies-arrayexpress

Non-Small Cell Lung Cancer patients undergoing radical radiotherapy

Project description:Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived >18 months were compared to the same time points from patients who survived <14 months using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform.

2018-10-19 | PXD001052 | Pride

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