Crucial role of CD69 in anti-tumor immunity through regulating the exhaustion of tumor-infiltrating T cells.

Abstract

The introduction of immune checkpoint inhibitors in cancer treatment highlights the negative regulation of anti-tumor immunity, such as effector T-cell exhaustion in the tumor microenvironment. However, the mechanisms underlying the induction and prevention of T-cell exhaustion remain largely unknown. We found that CD69, a type II glycoprotein known to regulate inflammation through T-cell migration and retention in tissues, plays an important role in inducing the exhaustion of tumor-infiltrating T cells. Cd69-/- mice showed reduced tumor growth and metastasis in a 4T1-luc2 murine breast cancer model, in which increased numbers of tumor-infiltrating lymphocytes, relatively little T-cell exhaustion, and enhanced IFNγ production were observed. Anti-CD69 monoclonal antibody treatment attenuated the T-cell exhaustion and tumor progression in tumor-bearing mice. These findings highlight a novel role of CD69 in controlling the tumor immune escape mediated by T-cell exhaustion and indicate that CD69 is a novel target for cancer immunotherapy.

• Authors: Yukiyoshi Mita, Motoko Y Kimura, Koji Hayashizaki, Ryo Koyama-Nasu, Toshihiro Ito, Shinichiro Motohashi, Yoshitaka Okamoto, Toshinori Nakayama
• Journal: International immunology (Int Immunol) Vol. 30 Issue 12 Pg. 559-567 (11 14 2018) ISSN: 1460-2377 [Electronic] England
• PMID: 30085193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• CD69 antigen
• Lectins, C-Type

Topics

• Animals
• Antigens, CD (immunology)
• Antigens, Differentiation, T-Lymphocyte (immunology)
• Breast Neoplasms (immunology, pathology)
• Cells, Cultured
• Female
• Lectins, C-Type (deficiency, immunology)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout