Beausang et al. performed TCR β-chain deep sequencing on lymphocytes from tumor tissue, adjacent normal tissue, and peripheral blood from 16 patients with early-stage breast cancer. While CDR3 repertoires overlapped within patients, tumor tissue had more lymphocyte infiltration, but less clonal diversity than normal breast tissue; tumor and normal tissue were also individually distinct from blood. Most abundant tumor-enriched clonotypes could be found in adjacent normal tissue and tissue from healthy volunteers, suggesting lack of tumor specificity.
Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing approximately 2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including approximately 50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment.
Author Info: (1) Department of Bioengineering, Stanford University, Stanford, CA 94305. (2) Department of Surgery, Stanford University School of Medicine, Stanford, CA (3) Department of Surgery
Author Info: (1) Department of Bioengineering, Stanford University, Stanford, CA 94305. (2) Department of Surgery, Stanford University School of Medicine, Stanford, CA (3) Department of Surgery, Stanford University School of Medicine, Stanford, CA (4) Department of Surgery, Stanford University School of Medicine, Stanford, CA (5) Department of Surgery, Stanford University School of Medicine, Stanford, CA (6) Department of Surgery, Stanford University School of Medicine, Stanford, CA (7) Department of Bioengineering, Stanford University, Stanford, CA 94305; quake@stanford.edu. Department of Applied Physics, Stanford University, Stanford, CA 94305. Chan Zuckerberg Biohub, San Francisco, CA 94518.
