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Increased neutrophil infiltration and lower prevalence of tumor mutation burden and microsatellite instability are hallmarks of RAS mutant colorectal cancers

Authors:

Emil Lou, Yasmine Baca, Joanne Xiu, Andrew Nelson, Subbaya Subramanian, Mohamed E Salem, Muhammad Shaalan Beg, Elisa Fontana, Maria Diab, Philip Agop Philip, Richard M. Goldberg, Ritu Pandey, Tobias Arkenau, Weijing Sun, Heinz-Josef Lenz, Anthony Frank Shields, Wafik S. El-Deiry, Wolfgang Michael Korn;

Background: The tumor microenvironment (TME) of colorectal cancers (CRC) is modulated by oncogenic drivers such as KRAS. The TME comprises a broad landscape of immune infiltration. What is less known is how tumor genomics associates with the immune cell landscape. The objective of this study was to characterize immune cell types in RAS wild-type (WT) and mutant (MT) CRC, and to examine the prevalence of immuno-oncologic (IO) biomarkers (e.g. tumor mutation burden (TMB), PD-L1, MSI-H/dMMR) in these tumors. We performed genomic and transcriptomic analysis to confirm associations of mutant RAS with immune infiltration of the TME conducive to metastasis vs. potential response to immunotherapies.

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