INTRA-TUMORAL INFILTRATION OF GZMKHIGH CD8+ T EFFECTOR MEMORY CELLS IS ASSOCIATED WITH POOR CLINICAL OUTCOME IN NON-METASTATIC COLORECTAL CANCER.

As with most solid tumor malignancies, CRC possess more than one major histological subtype that likely generate disparate immune responses. The heterogeneity in the immune cell response to CRC highlights the need to develop novel immune diagnostics that could predict the risk of disease relapse and devise a secondary strategy to address that risk. The purpose of this study was to prospectively provide a clear description of the patient-specific immune landscape present in CRC to target the dominant immune suppressive factors within a given tumor that may improve response rates while ushering in the age of personalized therapies for cancer patients. We described a functional interplay between neutrophils and CD8+ T cells that impacts on tumor immune escape and relapse. Specifically, we showed that tumor infiltrating neutrophils expressing high levels of CD15 interact with CD8+ T effector memory cells skewing them to produce GZMK, associated with tumor progression in CRC patients. Our fundings identify a unique immune signature, which might inform therapeutic decision making, possibly leading to new immunotherapeutic targets.