NKG2D-mediated cytotoxicity of CD4 cytotoxic T cells in multiple myeloma
Abstract
Abstract Emerging evidence indicates that CD4+ T cells contribute to antitumor immunity beyond their traditional roles as helpers or regulators. However, the specific subset of CD4+ T cells mediating beneficial outcomes in patients with multiple myeloma remains unclear. Here, we performed single-cell RNA sequencing and T-cell receptor sequencing on CD4+ T cells sorted from the bone marrow of patients across the stages of myeloma progression. We identified several distinct states of CD4+ cytotoxic T lymphocytes (CTLs) that were significantly increased and clonally expanded in patients with myeloma. CD4+ CTLs displayed transcriptional and phenotypic characteristics indicative of cytotoxicity, demonstrating their ability to directly kill myeloma cells. This cytotoxicity, however, was abrogated by NKG2D blockade. Notably, the abundance of NKG2D+CD4+ CTLs correlated with improved survival in patients with myeloma. Our findings suggest that harnessing CD4+ CTLs could lead to novel strategies for enhancing immunotherapy outcomes in multiple myeloma.
Article Details
Authors (20)
Sojeong Kim
Jeong-Eun Kwak
1Yonsei University College of Medicine, Seoul, South Korea
June-Young Koh
2Inocras Inc, San Diego, United States
Ji Eun Lee
Hye Won Kook
1Yonsei University College of Medicine, Seoul, South Korea
Minchae Kim
4Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea
Haerim Chung
1Yonsei University College of Medicine, Seoul, South Korea
Yu Ri Kim
Soo Jeong Kim
Jin Seok Kim
10Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
June-won Cheong
11Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Min Goo Lee
Brain Korea 21 project for Medical Science, Yonsei University College of Medicine
Hoyoung Lee
6Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
Su-Hyung Park
Eui-Cheol Shin
Saeam Shin
1Severance Hospital, Yonsei University College of Medicine, Department of Laboratory Medicine, Seoul, Korea
Sun Och Yoon
8Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
Il-Kyu Choi
4Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea
Jeong Seok Lee
Hyunsoo Cho
1Yonsei University College of Medicine, Seoul, South Korea