Skip to main content

Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.

Publication ,  Journal Article
Chongsathidkiet, P; Jackson, C; Koyama, S; Loebel, F; Cui, X; Farber, SH; Woroniecka, K; Elsamadicy, AA; Dechant, CA; Kemeny, HR; Cheema, TA ...
Published in: Nat Med
September 2018

T cell dysfunction contributes to tumor immune escape in patients with cancer and is particularly severe amidst glioblastoma (GBM). Among other defects, T cell lymphopenia is characteristic, yet often attributed to treatment. We reveal that even treatment-naïve subjects and mice with GBM can harbor AIDS-level CD4 counts, as well as contracted, T cell-deficient lymphoid organs. Missing naïve T cells are instead found sequestered in large numbers in the bone marrow. This phenomenon characterizes not only GBM but a variety of other cancers, although only when tumors are introduced into the intracranial compartment. T cell sequestration is accompanied by tumor-imposed loss of S1P1 from the T cell surface and is reversible upon precluding S1P1 internalization. In murine models of GBM, hindering S1P1 internalization and reversing sequestration licenses T cell-activating therapies that were previously ineffective. Sequestration of T cells in bone marrow is therefore a tumor-adaptive mode of T cell dysfunction, whose reversal may constitute a promising immunotherapeutic adjunct.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

September 2018

Volume

24

Issue

9

Start / End Page

1459 / 1468

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Spleen
  • Sphingosine
  • Mice, Inbred C57BL
  • Lysophospholipids
  • Lymphopenia
  • Lymphoid Tissue
  • Immunology
  • Humans
  • Glioblastoma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chongsathidkiet, P., Jackson, C., Koyama, S., Loebel, F., Cui, X., Farber, S. H., … Fecci, P. E. (2018). Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med, 24(9), 1459–1468. https://doi.org/10.1038/s41591-018-0135-2
Chongsathidkiet, Pakawat, Christina Jackson, Shohei Koyama, Franziska Loebel, Xiuyu Cui, S Harrison Farber, Karolina Woroniecka, et al. “Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.Nat Med 24, no. 9 (September 2018): 1459–68. https://doi.org/10.1038/s41591-018-0135-2.
Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med. 2018 Sep;24(9):1459–68.
Chongsathidkiet, Pakawat, et al. “Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.Nat Med, vol. 24, no. 9, Sept. 2018, pp. 1459–68. Pubmed, doi:10.1038/s41591-018-0135-2.
Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, Woroniecka K, Elsamadicy AA, Dechant CA, Kemeny HR, Sanchez-Perez L, Cheema TA, Souders NC, Herndon JE, Coumans J-V, Everitt JI, Nahed BV, Sampson JH, Gunn MD, Martuza RL, Dranoff G, Curry WT, Fecci PE. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med. 2018 Sep;24(9):1459–1468.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

September 2018

Volume

24

Issue

9

Start / End Page

1459 / 1468

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Spleen
  • Sphingosine
  • Mice, Inbred C57BL
  • Lysophospholipids
  • Lymphopenia
  • Lymphoid Tissue
  • Immunology
  • Humans
  • Glioblastoma