NIH VideoCast - NIH Director’s Seminar: The Power and Potential of the Microenvironment in Cancer Metastasis

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NIH Director’s Seminar: The Power and Potential of the Microenvironment in Cancer Metastasis

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Air date:	Friday, February 17, 2023, 12:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 274 (223 Live, 51 On-demand)
Category:	NIH Director's Seminars
Runtime:	00:55:47
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	NIH Director’s Seminar The tumor microenvironment – cellular and molecular changes in non-cancer cells and tissues –drive cancer progression. The pre-metastatic niche is the microenvironment important for metastatic initiation that is established at distant sites in response to primary tumor factors during cancer progression. We first characterized this microenvironment, which involves changes in both stromal and immune populations, in the pre-metastatic lungs of tumor-bearing mice. We have identified unique changes in these pre-metastatic sites by flow cytometry and RNA sequencing approaches, defining a gene signature of pre-metastatic niche formation that includes the upregulation of immune suppression genes consistent across different metastatic tissues, including lung and liver, as well as across species with commonalities in murine and human early metastatic microenvironments. Performing single cell RNA sequencing of the pre-metastatic niche revealed key immune suppression genes were found in the myeloid cell clusters. In addition to the increase of myeloid cells and immunosuppressive pathways, we discovered that T cell populations are reduced in pre-metastatic lungs. We hypothesized that reversing this immunosuppressive environment would restore T cell function and antitumor immunity. We designed a novel approach in which we generated Genetically Engineered Myeloid cells (GEMys) to deliver IL-12, a potent anti-tumor molecule, into the pre-metastatic microenvironment. Our studies demonstrate that IL12-GEMys can functionally modulate the core program of immune suppression in the pre-metastatic niche to successfully rebalance the dysregulated metastatic microenvironment in cancer. Therapies harnessing the power of the tumor microenvironment to modulate cancer progression can hold promise to effectively limit metastatic progression.

NLM Title:	The power and potential of the microenvironment in cancer metastasis / Rosandra Kaplan.
Author:	Kaplan, Rosandra.
Publisher:
Abstract:	(CIT): NIH Director"s Seminar The tumor microenvironment - cellular and molecular changes in non-cancer cells and tissues -drive cancer progression. The pre-metastatic niche is the microenvironment important for metastatic initiation that is established at distant sites in response to primary tumor factors during cancer progression. We first characterized this microenvironment, which involves changes in both stromal and immune populations, in the pre-metastatic lungs of tumor-bearing mice. We have identified unique changes in these pre-metastatic sites by flow cytometry and RNA sequencing approaches, defining a gene signature of pre-metastatic niche formation that includes the upregulation of immune suppression genes consistent across different metastatic tissues, including lung and liver, as well as across species with commonalities in murine and human early metastatic microenvironments. Performing single cell RNA sequencing of the pre-metastatic niche revealed key immune suppression genes were found in the myeloid cell clusters. In addition to the increase of myeloid cells and immunosuppressive pathways, we discovered that T cell populations are reduced in pre-metastatic lungs. We hypothesized that reversing this immunosuppressive environment would restore T cell function and antitumor immunity. We designed a novel approach in which we generated Genetically Engineered Myeloid cells (GEMys) to deliver IL-12, a potent anti-tumor molecule, into the pre-metastatic microenvironment. Our studies demonstrate that IL12-GEMys can functionally modulate the core program of immune suppression in the pre-metastatic niche to successfully rebalance the dysregulated metastatic microenvironment in cancer. Therapies harnessing the power of the tumor microenvironment to modulate cancer progression can hold promise to effectively limit metastatic progression.
Subjects:	Genetic Engineering--methods Myeloid Cells--physiology Neoplasm Metastasis--prevention & control RNA-Seq--methods Single-Cell Gene Expression Analysis--methods Tumor Microenvironment--physiology
Publication Types:	Lecture Webcast
NLM Classification:	QZ 200
NLM ID:	9918573157506676
CIT Live ID:	49152
Permanent link:	https://videocast.nih.gov/watch=49152

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