Summary
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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References
Joyce, J. A. & Fearon, D. T. T cell exclusion, immune privilege, and the tumor microenvironment. Science 348, 74–80 (2015).
Biasci, D., Smoragiewicz, M., Connell, C. M., Wang, Z., Gao, Y., Thaventhiran, J. E. D. et al. CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response. Proc. Natl Acad. Sci. USA 117, 28960–28970 (2020).
Feig, C., Jones, J. O., Kraman, M., Wells, R. J., Deonarine, A., Chan, D. S. et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc. Natl Acad. Sci. USA 110, 20212–20217 (2013).
Wang, Z., Yan, R., Li, J., Gao, Y., Moresco, P., Yao, M. et al. Pancreatic cancer cells assemble a CXCL12-keratin 19 coating to resist immunotherapy. Preprint at bioRxiv https://doi.org/10.1101/776419 (2020).
Chow, M. T., Ozga, A. J., Servis, R. L., Frederick, D. T., Lo, J. A., Fisher, D. E. et al. Intratumoral activity of the CXCR3 chemokine system is required for the efficacy of anti-PD-1 therapy. Immunity 50, 1498–1512 (2019).
McLane, L. M., Abdel-Hakeem, M. S. & Wherry, E. J. CD8 T cell exhaustion during chronic viral infection and cancer. Annu. Rev. Immunol. 37, 457–495 (2019).
Scott, A. C., Dündar, F., Zumbo, P., Chandran, S. S., Klebanoff, C. A., Shakiba, M. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270–274 (2019).
Lutz, E. R., Wu, A. A., Bigelow, E., Sharma, R., Mo, G., Soares, K. et al. Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol. Res. 2, 616–631 (2014).
Ford, K., Hanley, C. J., Mellone, M., Szyndralewiez, C., Heitz, F., Wiesel, P. et al. NOX4 inhibition potentiates immunotherapy by overcoming cancer-associated fibroblast-mediated CD8 T-cell exclusion from tumors. Cancer Res. 80, 1846–1860 (2020).
Kasashima, H., Duran, A., Martinez-Ordoñez, A., Nakanishi, Y., Kinoshita, H., Linares, J. F. et al. Stromal SOX2 upregulation promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population. Dev. Cell 56, S1534–S5807 (2020).
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The authors would like to acknowledge the contribution of Jordan A. Pearson who created Fig. 1.
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DTF contributed to the conception of the work and drafted the manuscript. KD contributed to the writing of the paper. Both authors approved the final version.
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Fearon, D.T., Janowitz, T. AMD3100/Plerixafor overcomes immune inhibition by the CXCL12–KRT19 coating on pancreatic and colorectal cancer cells. Br J Cancer 125, 149–151 (2021). https://doi.org/10.1038/s41416-021-01315-y
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DOI: https://doi.org/10.1038/s41416-021-01315-y
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