Clinical relevance of circulating mucosal-associated invariant T cell levels and their anti-cancer activity in patients with mucosal-associated cancer

Abstract

// Eun Jeong Won 1,* , Jae Kyun Ju 2,* , Young-Nan Cho 3,* , Hye-Mi Jin 3 , Ki-Jeong Park 3 , Tae-Jong Kim 3 , Yong-Soo Kwon 4 , Hae Jin Kee 5 , Jung-Chul Kim 2 , Seung-Jung Kee 1 and Yong-Wook Park 3 1 Department of Laboratory Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea 2 Department of Surgery, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea 3 Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea 4 Department of Pulmonary and Critical Care Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea 5 Heart Research Center, Chonnam National University Hospital, Gwangju, Republic of Korea * These authors have contributed equally to this work Correspondence to: Yong-Wook Park, email: // Seung-Jung Kee, email: // Keywords : cytotoxicity, chemokine, migration, mucosal-associated invariant T cells, mucosal-associated cancer Received : March 23, 2016 Accepted : July 27, 2016 Published : August 10, 2016 Abstract Mucosal-associated invariant T (MAIT) cells are an antimicrobial MR1-restricted T cell subset and play an important role in immune defense response to bacteria. However, little is known about the role of MAIT cells in cancer. The aims of this study were to examine the level and function of MAIT cells in cancer patients and to evaluate the clinical relevance of MAIT cell levels. Ninety-nine patients with cancer and 20 healthy controls were included in this study. Circulating MAIT cell levels were significantly reduced in patients with mucosal-associated cancers (MACs), such as gastric, colon and lung cancers, but their capacities for IFN-γ, IL-17, or TNF-α production were preserved. This MAIT cell deficiency was significantly correlated with N staging and carcinoembryonic antigen level. Percentages of MAIT cells were significantly higher in cancer tissue than in peripheral blood and immunofluorescent labeling showed MAIT cell infiltration into colon cancer tissues. Circulating MAIT cells exhibited high levels of CCR6 and CXCR6, and their corresponding chemokines, such as CCL20 and CXCL16, were strongly expressed in colon cancer tissues. Activated MAIT cells not only had lymphokine-activated killer activity, but they also had direct cytotoxicity on K562 cells via degranulation of granzyme B and perforin. This study primarily demonstrates that circulating MAIT cells are reduced in MAC patients due to migration to mucosal cancer tissues and they have the potential to kill cancer cells. In addition, this circulating MAIT cell deficiency is related to the degree of cancer progression in mucosal tissues.