POSTER: Comprehensive Image Analysis Of Immunostained NSCLC Tissues Provides Necessary Context For Immune Oncology Biomarker Profiling

ABSTRACT

Manual pathology assessments of Immunohistochemistry (IHC) markers in immuneoncology (IO) is often challenging and results can be highly variable. Measuring biomarker presence in IO must take in to account both immune and tumor environments and provide contextual information on the interaction between tumor and immune biomarker landscapes. Due to the complex nature surrounding tissue biomarker interpretation in IO, digital image analysis (IA) solutions have been developed that layer complex artificial intelligence (AI) and machine learning algorithms to obtain full tissue biomarker profiles necessary for drug development and patient stratification.

Here, a comprehensive tissue analysis solution is presented in monoplex PD-L1 and CD8 stained slides that includes precise digital biomarker scoring in tumor and stromal compartments, recapitulation of common scoring paradigms, analysis of biomarker expression at the tumor/stroma interface (margin), and quantifi cation, scoring, and spatial localization of lymphocytes in the tumor and stroma. Aggregation of all cellular and biomarker data generates tissue phenotypes that characterize the IO landscape of each tissue.

RESULTS & CONCLUSIONS

In this study it is demonstrated that integration of methodically implemented image analysis algorithms with clinical oversight results in large per-tissue datasets. Each successive implementation of cell stratification results in higher complexity of the image analysis dataset that can be used to draw conclusions beyond the capability of manual pathologist scoring.

In this study of a limited cohort of 20 NSCLC tissues, we found that PD-L1 and CD8 expression are positively correlated within each stratified tissue compartment, though PD-L1 expression showed no significant correlation with total counts of immune infiltrate. Conversely, CD8 expression showed a negative correlation with total immune infiltrate as measured by both measures of positivity in the tumor as well as CD8 positive percentages of total immune infiltrate. This data suggests that a higher presence of CD8- immune cells within the tumor microenvironment have an immunosuppressive effect, likely mediated by a higher population of CD4+ T cells. It is thus important to consider not only CD8 presence, but CD8 in the context of total immune infiltrate, in order to understand inflamed, excluded, or ignorant phenotypes within the context of a balanced or imbalanced CD8 ratio.

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