Open AccessThe adhesion molecule ICAM-1 in diffuse large B-cell lymphoma post-rituximab era: relationship with prognostic importance and rituximab resistance
Author(s) -
Yizhen Liu,
Juan Gu,
Ling Yang,
Ping-Chiao Tsai,
Ye Guo,
Kai Xue,
Zhihao Xia,
Xiaojian Liu,
Fangfang Lv,
Junning Cao,
Xin Hong,
Cory Mavis,
Francisco J. HernandezIlizaliturri,
Qunling Zhang
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202180
Subject(s) - rituximab , diffuse large b cell lymphoma , lymphoma , cell adhesion molecule , cell adhesion , medicine , cancer research , oncology , adhesion , immunology , chemistry , organic chemistry
Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface receptor contributing to lymphocyte homing, adhesion and activation. The prognostic significance of the protein is unknown in diffuse large B-cell lymphoma (DLBCL) in post-rituximab era. We detected expression of ICAM-1 immunohistochemically in 102 DLBCL tissue samples. Overexpression of ICAM-1 was found in 28 (27.5%) cases. In patients with low ICAM-1 expression levels, the addition of rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy resulted in an improved overall response rate, progression-free survival (PFS) and overall survival (OS) ( P =0.019, 0.01, 0.02). In pre-clinical models, we found that chronic exposure of cell lines to rituximab led to downregulation of ICAM-1 and acquirement of a rituximab resistant phenotype. In vitro exposure of rituximab resulted in rapid aggregation of B-cells regardless of the ICAM-1 expression levels. MTT assay showed knockdown of ICAM-1 could cause rituximab resistance. Neutralization of ICAM-1 did not affect rituximab activity in vitro and in vivo. Our data illustrated that in post-rituximab era, R-CHOP significantly improved the ORR, PFS and OS in ICAM-1 negative subset patients. Downregulation of ICAM-1 may contribute to rituximab resistance, and that rituximab, by promoting cell-cell aggregation, may sensitize cells to the cytotoxic effects of chemotherapy agents.