CXCL4 mediates tumor regrowth after chemotherapy by suppression of antitumor immunity.

Abstract:

:The recurrence of colorectal cancer after chemotherapy is the leading cause of its high mortality. We propose that elucidating the mechanisms of tumor regrowth after chemotherapy in tumor-bearing mice may provide new insights into tumor relapse in cancer patients. We firstly report the identification of a chemokine, CXCL4, that plays an important role in the molecular mechanism of cancer regrowth after chemotherapy. A syngenic transplantation tumor model was established with murine colon cancer CT26 cells and treated with 5-FU. Genome-wide gene expression analysis determined that CXCL4 was transiently upregulated in the tumor model. Systemic overexpression of CXCL4 accelerated cancer growth in vivo, but not in vitro. Conversely, the anti-CXCL4 monoclonal antibody (CXCL4-mab) retarded tumor-regrowth after 5-FU treatment in immune-competent mice, but not nude mice. The CXCL4-mab treatment increased the local expression levels of IFN-γ and Gran-b genes in the tumor-bed, and elevated the function of CTLs against CT26 cells. Thus, the colon cancer cells in responding to the cytotoxic stress of 5-FU produce a high level of CXCL4, which suppresses antitumor immunity to confer the residual cancer cells an advantage for regrowth after chemotherapy. Our findings provide a novel target for developing therapeutics aiming to increase antitumor immunity after chemotherapy.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Zhang Y,Gao J,Wang X,Deng S,Ye H,Guan W,Wu M,Zhu S,Yu Y,Han W

doi

10.1080/15384047.2015.1095404

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

1775-83

issue

12

eissn

1538-4047

issn

1555-8576

journal_volume

16

pub_type

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