Comparison of infiltrating lymphocytes in colon tumor versus adjacent normal mucosal tissue (P2179)

Abstract

Abstract Tumor immunogenicity is emerging as an important but incompletely understood contributor to cancer progression. Tumors from colorectal cancer (CRC) are generally immunogenic and commonly infiltrated with T lymphocytes. However, the details of the adaptive immune reaction to these tumors are poorly understood. We have accrued both colon tumor samples and adjacent healthy mucosal samples from 15 CRC patients to study lymphocytes infiltrating these tissues. We apply a method for detailed sequencing of T-cell receptor (TCR) sequences from tumor infiltrating lymphocytes (TILs) in CRC tumors at high throughput to probe T-cell clones in comparison to the TCRs from adjacent healthy mucosal tissue. The variation in diversity of the TIL repertoire was far wider than the variation of T-cell clones in the healthy mucosa, and the oligoclonality was higher on average in the tumors. However, the diversity of the T-cell repertoire in both CRC tumors and healthy mucosa was on average 100-fold lower than in peripheral blood. Using the TCR sequences to identify and track clones between mucosal and tumor samples, we determined that the immune response in the tumor is different than in the adjacent tissue, and the number of shared clones are not dependent on distance between the tissues. Together, these data imply that CRC tumors induce a specific adaptive immune response, but that this response differs widely in strength and breadth between patients.