T cell receptor β-chain repertoire analysis of tumor infiltrating lymphocytes in pancreatic cancer.

Pancreatic cancer is lethal due to lack of perceptible symptoms and effective treatment methods. Immunotherapy may provide promising therapeutic choices for malignant tumors like pancreatic cancer. Tumor infiltrating lymphocytes (TILs) in tumor mesenchyme could recognize peptide antigens presented on the surface of tumor cells. This study aimed to test the relationship between the TCR β repertoire of the tumor and peripheral blood, and also to investigate the intra-tumor spatial heterogeneity of the TCR β repertoire in pancreatic cancer. To the best of our knowledge, this is the first study to evaluate the clonal composition of TCR β repertoire in TILs across the spatial extent of pancreatic cancer. In this study, we studied five patients who were diagnosed with primary pancreatic cancer. Ultra-deep sequencing was used to assess the rearrangement of the TCR β-chain (TCR β) gene. HE staining and immunohistochemistry of CD3, CD4, CD8 and HLA class I were used to show histopathology and immune conditions macroscopically. TILs repertoire showed that different regions of the same tumor showed a greater number of repertoire overlaps between each other than between peripheral blood, which suggested that T cell clones in pancreatic cancer might be quite different from those in peripheral blood. Whereas, intra-tumoral TCR β repertoires were spatially homogeneous between different regions of a single tumor tissue. Based on these results, we speculated that the cellular adaptive immune response in pancreatic cancer was found to be spatially homogeneous, and this may pave way for immunotherapy for the treatment of pancreatic cancer patients. This article is protected by copyright. All rights reserved.