Abstract C108: Quantifying PD-L1 spatial distribution signatures for patient selection approaches
Authors: Krueger Joseph S. , Martin Nathan , Milici Anthony , Aeffner Famke 
Published: May 2016

Inhibitors of inflammatory checkpoints, such as PD-L1 inhibitors, have demonstrated great promise in preclinical and clinical studies. This therapeutic paradigm focuses on controlling natural inflammatory checkpoints to stimulate an elevated inflammatory response against the tumor to increase anti-tumor inflammatory cell infiltrates in the tumor microenvironment or decrease inflammatory suppressor infiltrates. The proteins which control these processes can be found in the tumor cells, cells in the tumor micro-environment (TME), or in both locales. Positive cells are often assessed in a qualitative or semi-quantitative manner using immunohistochemistry and evaluation of a limited number of representative microscopy fields across a particular tissue compartment (tumor vs stroma) or the whole tissue area. However, the locale of the inflammatory suppressors such as PD-L1 may be more revealing than estimating the tumor-wide dispersion of an inflammatory cell type. Unfortunately, the intricate spatial relationships and the often complex distribution of inflammatory cells in tissues pose significant challenges for a meaningful evaluation.

We have developed an approach which can quantify these spatial relationship in a contextual, biologically meaningful score. Immunohistochemistry staining for PD-L1 in whole lung cancer tissue sections was performed, and our CellMap software was used to assess inflammatory cell distribution in the whole tissue sections. PD-L1 positive cells were quantified relative to: 1) the total number of cells in the tumor and stromal tissue compartments, and 2) the number of cells within a distance from the tumor/stroma interface. Interestingly, several unique PD-L1 distribution patterns relative to the tumor/stroma interface were observed in the sample cohort analyzed. Quantifying the distribution of PD-L1 positive cells as a function of distance from the tumor/stroma interface revealed distribution signatures, which could be used to differentiate between samples. In contrast, this differentiation of the same samples was not possible when PD-L1 cells were assessed relative to the total number of cells.

This study provided a novel method for assessing inflammatory cell type spatial distribution relative to a tissue feature, the tumor/stroma interface. The data suggested that unique spatial patterns of inflammatory cell type distribution could be used to uniquely stratify patients compared to existing quantitative methods. Taken together, this proof-of-concept study demonstrates a unique quantitative assessment of inflammatory cell infiltrates in tumors that could be used to gain new insights into inflammatory cell type distributions and interactions in tumors, inflammatory cell spatial responses to oncology therapies, and novel patient selection criteria for traditional and immuno-oncology therapeutics.

Citation Format: Joseph S. Krueger, Nathan Martin, Anthony Milici, Famke Aeffner. Quantifying PD-L1 spatial distribution signatures for patient selection approaches. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C108.