2. Academic Validation
  3. CD106 in tumor-specific exhausted CD8+ T cells mediates immunosuppression by inhibiting TCR signaling

CD106 in tumor-specific exhausted CD8+ T cells mediates immunosuppression by inhibiting TCR signaling

  • Cancer Res. 2024 Apr 18. doi: 10.1158/0008-5472.CAN-23-0453.
Yuto Naoi 1,  Takao Morinaga 2,  Joji Nagasaki 3,  Ryo Ariyasu 4,  Youki Ueda 5,  Kazuo Yamashita 6,  Wenhao Zhou 3,  Shusuke Kawashima 7,  Katsushige Kawase 8,  Akiko Honobe-Tabuchi 9,  Takehiro Ohnuma 9,  Tatsuyoshi Kawamura 9,  Yoshiyasu Umeda 10,  Yu Kawahara 11,  Yasuhiro Nakamura 12,  Yukiko Kiniwa 13,  Osamu Yamasaki 14,  Satoshi Fukushima 15,  Masahito Kawazu 16,  Yutaka Suzuki 17,  Hiroyoshi Nishikawa 18,  Toyoyuki Hanazawa 19,  Mizuo Ando 5,  Takashi Inozume 7,  Yosuke Togashi 3
Affiliations

Affiliations

  • 1 Okayama University, Japan.
  • 2 Chiba Cancer Center, Chiba, Chiba, Japan.
  • 3 Okayama University, Okayama, Japan.
  • 4 Japanese Foundation For Cancer Research, Tokyo, Japan.
  • 5 Okayama University, Okayama, Okayama, Japan.
  • 6 KOTAI Biotechnologies, Inc., Suita, Japan.
  • 7 Chiba University, Chiba, Chiba, Japan.
  • 8 Chiba Cancer Center, Chiba-shi, Chiba, Japan.
  • 9 University of Yamanashi, Yamanashi, Japan.
  • 10 Saitama Medical University, Japan.
  • 11 Chiba University, Chiba, Japan.
  • 12 Saitama Medical University, Saitama, Japan.
  • 13 Shinshu University School of Medicine, Matsumoto, Japan.
  • 14 Shimane University Hospital, Izumo city, Shimane Pref., Japan.
  • 15 Kumamoto University, Kumamoto, Kumamoto, Japan.
  • 16 Chiba Cancer Center, Chiba, Japan.
  • 17 The University of Tokyo, Kashiwa, Chiba, Japan.
  • 18 National Cancer Centre, Chuo-ku, Tokyo, Japan.
  • 19 Graduate School of Medicine, Chiba University, Chiba, Japan.
PMID: 38635899 DOI: 10.1158/0008-5472.CAN-23-0453
Abstract

T cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T cell exhaustion, such as PD-1, can reinvigorate tumor-specific T cells and activate anti-tumor immunity in various types of Cancer. Here, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA-sequencing. High CD106 expression in the TME in clinical samples corresponded to improved response to Cancer Immunotherapy. CD106 in tumor-specific T cells suppressed anti-tumor immunity both in vitro and in vivo, and loss of CD106 in CD8+ T cells suppressed tumor growth and improved response to PD-1 blockade. Mechanistically, CD106 inhibited T-cell receptor (TCR) signaling by interacting with the TCR/CD3 complex and reducing its surface expression. Together, these findings provide insights into the immunosuppressive role of CD106 expressed in tumor-specific exhausted CD8+ T cells, identifying it as a potential biomarker and therapeutic target for Cancer Immunotherapy.

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