Webinar: Spatial Characterization of the Lung Tumor Microenvironment in Response to KRAS G12C Inhibition

KRAS G12C is the driving oncogenic mutation in ~10% of all non-small cell lung cancer (NSCLC) patients. The first inhibitor targeting this mutation was recently approved for the treatment of locally advanced or metastatic NSCLC. While this inhibitor targets the tumor cells specifically, changes in the immune infiltrate have been observed. In this webinar, Dr. Febe van Maldegem of Dr. Julian Downward's group at The Francis Crick Institute, will discuss the group's development of an Imaging Mass Cytometry (IMC) workflow that enables them to phenotypically and spatially characterize the tumor microenvironment (TME) in mouse tissues. Using this approach, they have shown how targeted KRAS G12C inhibition leads to a dramatic remodeling of the lung tumor microenvironment.

What you will learn:

• What changes can be observed in response to KRAS G12C inhibition
• How to apply imaging mass cytometry to mouse tissues
• How to optimize and automate downstream image segmentation
• How we can interrogate cell phenotypes and spatial relationships

Additional Q&A With Dr. Febe van Maldegem

Due to great interest in this talk, some submitted questions weren’t answered during the webinar. Dr. van Maldegem graciously answered these questions, below.

1. MRTX = ?

MRTX1257, is one of Mirati’s KRAS-G12C selective & covalent inhibitors.

2. Could you please explain more about your methodology?

We have not inhibited KRAS in the tumor microenvironment, but only in the tumor cells which carry the G12C mutation. This block in signaling leads to changes in gene expression by the tumor cells, which indirectly has effects on the TME.

3. How do you choose the right place for an antibody in the panel?

Most important factor is the brightness of the marker. Dimmer markers are best placed in the most sensitive range of the detector, between masses of 160-175. Spillover is not as much of a problem as with fluorophores, but there is a certain level of impurity of the metals that means that in particular isotopes of the same metal will give some spillover. With good panel design spillover can be minimized. Therefore, avoid placing very bright markers next to dim markers. The brightness of a directly APC-conjugated antibody in immunofluorescence is fairly predictable for its detectability in IMC.