Abstract 89P
Background
Colorectal cancer (CRC) remains a challenging and deadly disease with high tumor microenvironment (TME) heterogeneity. It is now understood that the TME is intricately linked to the tumor biology, response to therapy and clinical outcomes in CRC. For instance, an immunosuppressive TME can serve as a critical indicator of tumor progression.
Methods
Using a MultiOmyx hyperplex panel and deep learning based spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in 40 CRC patient samples with known MSI status. The MultiOmyx hyperplex panel focuses on detection of different categories of immune and stromal components such as T cells, B cells, macrophages, natural killer cells, dendritic cells and cancer-associated fibroblasts. With this hyperplex panel, we evaluated the level of expression and localization of different tumor infiltrating lymphocytes (TIL) and checkpoint modulators within the TME. The quantity, distribution and maturity of tertiary lymphoid structure (TLS) was also characterized in these 40 CRC patient samples.
Results
In summary, we found that the CRC tissues with different MSI status exhibited varying TMEs. The TME of the microsatellite instability high (MSI-H) CRC samples displayed more enriched CD4+, CD8+ and CD45RO+ T cells than the microsatellite-stable (MSS) CRC samples. Further, more mature TLS was detected in the MSI-H CRC samples than the MSS CRC ones. These data support that these MSI-H CRC samples showed a TME with distinct anti-tumor features including greater ability to recruit infiltration of immune cells and formation of mature TLS. Interestingly, these MSI-high samples also exhibited higher expression of checkpoint inhibitor receptors and their ligands.
Conclusions
The MultiOmyx hyperplex assay enables quantification of TLS, PD-L1 expression and TIL abundance from one single FFPE slide. The rich dataset provides holistic view of the immune contexture and spatial organization within the TME. These findings may have broad application and help identify biomarker signatures with improved prognostic value and predictive performance to immunotherapy in CRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
NeoGenomics.
Disclosure
Q. Au, H. Nunns, E. Parnell, K. Gallagher, E. Leones, F. Sahafi, V. Chizhevsky: Financial Interests, Personal, Full or part-time Employment: NeoGenomics.