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. Online ahead of print.ABSTRACTT 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.PMID:38635899 | DOI:10.1158/0008-5472.CAN-23-0453

Source: Cell Research - April 18, 2024 Category: Cytology Authors: Yuto Naoi Takao Morinaga Joji Nagasaki Ryo Ariyasu Youki Ueda Kazuo Yamashita Wenhao Zhou Shusuke Kawashima Katsushige Kawase Akiko Honobe-Tabuchi Takehiro Ohnuma Tatsuyoshi Kawamura Yoshiyasu Umeda Yu Kawahara Yasuhiro Nakamura Yukiko Kiniwa Osamu Yamasa Source Type: research