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Comment
. 2021 Jul;125(2):149-151.
doi: 10.1038/s41416-021-01315-y. Epub 2021 Mar 26.

AMD3100/Plerixafor overcomes immune inhibition by the CXCL12-KRT19 coating on pancreatic and colorectal cancer cells

Douglas T Fearon  1   2 , Tobias Janowitz  3   4
Affiliations
Comment

AMD3100/Plerixafor overcomes immune inhibition by the CXCL12-KRT19 coating on pancreatic and colorectal cancer cells

Douglas T Fearon et al. Br J Cancer. 2021 Jul.

Abstract

A recent Phase 1 clinical study of the immunological effects of inhibiting the chemokine receptor, CXCR4, in patients with pancreatic ductal adenocarcinoma or colorectal cancer suggests that stimulation of CXCR4 on immune cells suppresses the intratumoural immune reaction. Here, we discuss how CXCR4 mediates this response, and how cancer cells elicit it.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Blocking CXCR4 with AMD3100 allows T cell killing of CXCL12-coated cancer cells.
Left panel Cancer-associated fibroblasts (CAFs) in the tumour secrete CXCL12, which reversibly binds to KRT19 on the surface of PDA and CRC cancer cells. Cancer cell-derived TGM2 then covalently crosslinks the two proteins. Middle panel The CXCL12–KRT19 heterodimers stimulate CXCR4 on adjacent T cells to inhibit the ability of CXCR3 to mediate their infiltration into cancer cell nests. Right panel Administration of AMD3100 blocks the interaction between the cancer cell-associated CXCL12–KRT19 heterodimers with CXCR4 on T cells and allows their CXCR3 to respond to CXCL9/10/11 to mediate the accumulation of T cells in cancer cell nests.
See this image and copyright information in PMC

Comment on

  • CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response.
    Biasci D, Smoragiewicz M, Connell CM, Wang Z, Gao Y, Thaventhiran JED, Basu B, Magiera L, Johnson TI, Bax L, Gopinathan A, Isherwood C, Gallagher FA, Pawula M, Hudecova I, Gale D, Rosenfeld N, Barmpounakis P, Popa EC, Brais R, Godfrey E, Mir F, Richards FM, Fearon DT, Janowitz T, Jodrell DI. Biasci D, et al. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28960-28970. doi: 10.1073/pnas.2013644117. Epub 2020 Oct 30. Proc Natl Acad Sci U S A. 2020. PMID: 33127761 Free PMC article.

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