Citation

BibTex format

@article{Khan:2018:10.1172/JCI97454,
author = {Khan, AB and Carpenter, B and Santos, e Sousa P and Pospori, C and Khorshed, R and Griffin, J and Velica, P and Zech, M and Ghorashian, S and Forrest, C and Thomas, S and Anton, SG and Ahmadi, M and Holler, A and Flutter, B and Ramirez-Ortiz, Z and Means, TK and Bennett, CL and Stauss, H and Morris, E and Lo, Celso C and Chakraverty, R},
doi = {10.1172/JCI97454},
journal = {Journal of Clinical Investigation},
pages = {2010--2024},
title = {Redirection to the bone marrow improves T cell persistence and antitumor functions},
url = {http://dx.doi.org/10.1172/JCI97454},
volume = {128},
year = {2018}
}
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TY  - JOUR
AB  - A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration toward vascular-associated CXCL12+ cells in the BM and increased their local engraftment. Increased access of TCXCR4 to the BM microenvironment induced IL-15–dependent homeostatic expansion and promoted the differentiation of memory precursor–like cells with low expression of programmed death-1, resistance to apoptosis, and a heightened capacity to generate polyfunctional cytokine-producing effector cells. Following transfer to lymphoma-bearing mice, TCXCR4 showed a greater capacity for effector expansion and better tumor protection, the latter being independent of changes in trafficking to the tumor bed or local out-competition of regulatory T cells. Thus, redirected homing of T cells to the BM confers increased memory differentiation and antitumor immunity, suggesting an innovative solution to increase the persistence and functions of therapeutic T cells.
AU  - Khan,AB
AU  - Carpenter,B
AU  - Santos,e Sousa P
AU  - Pospori,C
AU  - Khorshed,R
AU  - Griffin,J
AU  - Velica,P
AU  - Zech,M
AU  - Ghorashian,S
AU  - Forrest,C
AU  - Thomas,S
AU  - Anton,SG
AU  - Ahmadi,M
AU  - Holler,A
AU  - Flutter,B
AU  - Ramirez-Ortiz,Z
AU  - Means,TK
AU  - Bennett,CL
AU  - Stauss,H
AU  - Morris,E
AU  - Lo,Celso C
AU  - Chakraverty,R
DO  - 10.1172/JCI97454
EP  - 2024
PY  - 2018///
SN  - 0021-9738
SP  - 2010
TI  - Redirection to the bone marrow improves T cell persistence and antitumor functions
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI97454
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000431959100028&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/70074
VL  - 128
ER  -
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