Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer

• Published in: Oncotarget 2018-01, Vol.9 (3), p.3805-3814
• Main Authors: Ren, Lili, Matsuda, Tatsuo, Deng, Boya, Kiyotani, Kazuma, Kato, Taigo, Park, Jae-Hyun, Seiwert, Tanguy Y, Vokes, Everett E, Agrawal, Nishant, Nakamura, Yusuke
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.23454

Though adoptive tumor-infiltrating lymphocyte (TIL) therapy has been explored in clinical trials for many years, there is little information for the clonotype composition between TILs in original tumor tissues and TILs that were expanded and infused to cancer patients. To investigate the similarity/difference in TILs in original tumor tissues and those of expanded populations in squamous cell carcinoma of head and neck (SCCHN) as well as their correlation with somatic mutations in cancer cells, we performed whole exome analysis, expression profile analysis of immune-related genes, and T cell receptor (TCR) analysis of original TILs and expanded TILs in 8 surgically-resected HPV-negative fresh tumors with SCCHN. We found an unusually high number of non-synonymous somatic mutations (4290, 1779 and 901 mutations) in three SCCHN tumors, in which we identified mutations in mismatch repair genes, or , or a DNA polymerase gene, . Interestingly, dominant TCR clonotypes of expanded CD8 TILs derived from these three tumors revealed high similarity to those in original tumors while for remaining tumors with the lower mutational load, we found that T cell clonotypes between TILs in original tumor tissues and those expanded were almost entirely different. Our findings might provide clinically useful information for identification of tumor-antigen-specific T cell clones that may lead to further improvement of adoptive TIL therapy for SCCHN patients.