Oncotarget

Research Papers:

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

Lili Ren, Tatsuo Matsuda, Boya Deng, Kazuma Kiyotani, Taigo Kato, Jae-Hyun Park, Tanguy Y. Seiwert, Everett E. Vokes, Nishant Agrawal, Yusuke Nakamura _

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Oncotarget. 2018; 9:3805-3814. https://doi.org/10.18632/oncotarget.23454

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Abstract

Lili Ren1,4, Tatsuo Matsuda1, Boya Deng1, Kazuma Kiyotani3, Taigo Kato1, Jae-Hyun Park1, Tanguy Y. Seiwert1, Everett E. Vokes1, Nishant Agrawal2 and Yusuke Nakamura1,2

1Department of Medicine, The University of Chicago, Chicago, IL, USA

2Department of Surgery, The University of Chicago, Chicago, IL, USA

3Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan

4Cytotherapy Laboratory, Shenzhen People’s Hospital (The second Clinical Medical College of Jinan University), Shenzhen, China

Correspondence to:

Yusuke Nakamura, email: ynakamura@bsd.uchicago.edu

Keywords: mismatch repair; non-synonymous mutation; squamous cell carcinoma of head and neck cancer; T cell receptor; tumor-infiltrating lymphocytes

Received: November 11, 2017    Accepted: December 10, 2017    Published: December 19, 2017

ABSTRACT

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 in vitro expanded and infused to cancer patients. To investigate the similarity/difference in TILs in original tumor tissues and those of in vitro 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 in vitro 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, MSH2 or MSH4, or a DNA polymerase gene, POLE. 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 in vitro 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.


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