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Table S3 from CD69 Imposes Tumor-Specific CD8+ T-cell Fate in Tumor-Draining Lymph Nodes

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posted on 2023-08-03, 08:20 authored by Ryo Koyama-Nasu, Motoko Y. Kimura, Masahiro Kiuchi, Ami Aoki, Yangsong Wang, Yukiyoshi Mita, Ichita Hasegawa, Yukihiro Endo, Atsushi Onodera, Kiyoshi Hirahara, Shinichiro Motohashi, Toshinori Nakayama

Table S3

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Ministry of Education, Culture, Sports, Science and Technology (MEXT)

Japan Agency for Medical Research and Development (AMED)

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ARTICLE ABSTRACT

Tumor-specific CD8+ T cells play a pivotal role in antitumor immunity and are a key target of immunotherapeutic approaches. Intratumoral CD8+ T cells are heterogeneous; Tcf1+ stemlike CD8+ T cells give rise to their cytotoxic progeny—Tim-3+ terminally differentiated CD8+ T cells. However, where and how this differentiation process occurs has not been elucidated. We herein show that terminally differentiated CD8+ T cells can be generated within tumor-draining lymph nodes (TDLN) and that CD69 expression on tumor-specific CD8+ T cells controls its differentiation process through regulating the expression of the transcription factor TOX. In TDLNs, CD69 deficiency diminished TOX expression in tumor-specific CD8+ T cells, and consequently promoted generation of functional terminally differentiated CD8+ T cells. Anti-CD69 administration promoted the generation of terminally differentiated CD8+ T cells, and the combined use of anti-CD69 and anti–programmed cell death protein 1 (PD-1) showed an efficient antitumor effect. Thus, CD69 is an attractive target for cancer immunotherapy that synergizes with immune checkpoint blockade.

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