Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2012 Sep 27;2(3):628-39. doi: 10.1016/j.celrep.2012.08.006. Epub 2012 Sep 6.

Immune tolerance to tumor antigens occurs in a specialized environment of the spleen.

Author information

  • 1Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy.

Abstract

Peripheral tolerance to tumor antigens (Ags) is a major hurdle for antitumor immunity. Draining lymph nodes are considered the privileged sites for Ag presentation to T cells and for the onset of peripheral tolerance. Here, we show that the spleen is fundamentally important for tumor-induced tolerance. Splenectomy restores lymphocyte function and induces tumor regression when coupled with immunotherapy. Splenic CD11b(+)Gr-1(int)Ly6C(hi) cells, mostly comprising proliferating CCR2(+)-inflammatory monocytes with features of myeloid progenitors, expand in the marginal zone of the spleen. Here, they alter the normal tissue cytoarchitecture and closely associate with memory CD8(+) T cells, cross-presenting tumor Ags and causing their tolerization. Because of its high proliferative potential, this myeloid cell subset is also susceptible to low-dose chemotherapy, which can be exploited as an adjuvant to passive immunotherapy. CCL2 serum levels in cancer patients are directly related to the accumulation of immature myeloid cells and are predictive for overall survival in patients who develop a multipeptide response to cancer vaccines.

Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

PMID:
22959433
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk