PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes

• Nagasaki, Joji

• Inozume, Takashi

• Sax, Nicolas

• Ariyasu, Ryo

• Ishikawa, Masakazu

• Yamashita, Kazuo

• Kawazu, Masahito

• Ueno, Toshihide

• Irie, Takuma

• Tanji, Etsuko

• Morinaga, Takao

• Honobe, Akiko

• Ohnuma, Takehiro

• Yoshino, Mitsuru

• Iwata, Takekazu

• Kawase, Katsushige

• Sasaki, Keita

• Hanazawa, Toyoyuki

• Kochin, Vitaly

• Kawamura, Tatsuyoshi

• Matsue, Hiroyuki

• Hino, Masayuki

• Mano, Hiroyuki

• Suzuki, Yutaka

• Nishikawa, Hiroyoshi

• Togashi, Yosuke

Abstract

PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (T-ex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the T-ex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the T-ex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such T-ex clonotypes, mainly from TDLNs.

Journal

• Cell Reports

  Cell Reports 38 (5), 110331-, 2022-02-01

  Cell Press

Keywords

• General Biochemistry, Genetics and Molecular Biology

Details

• CRID: 1050854108010022656
• NII Article ID: 120007192058
• ISSN: 22111247
• DOI: 10.1016/j.celrep.2022.110331
• Web Site: https://ousar.lib.okayama-u.ac.jp/63200
• Web Site: https://api.elsevier.com/content/article/PII:S221112472200047X?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S221112472200047X?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
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  • Crossref
  • CiNii Articles
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