Galectin-1-driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance

Dhanya K. Nambiar, Todd Aguilera, Hongbin Cao, Shirley Kwok, Christina Kong, Joshua Bloomstein, Zemin Wang, Vangipuram S. Rangan, Dadi Jiang, Rie Von Eyben, Rachel Liang, Sonya Agarwal, A. Dimitrios Colevas, Alan Korman, Clint T. Allen, Ravindra Uppaluri, Albert C. Koong, Amato Giaccia, Quynh Thu Le

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Immune checkpoint inhibitors (ICIs), although promising, have variable benefit in head and neck cancer (HNC). We noted that tumor galectin-1 (Gal1) levels were inversely correlated with treatment response and survival in patients with HNC who were treated with ICIs. Using multiple HNC mouse models, we show that tumor-secreted Gal1 mediates immune evasion by preventing T cell migration into the tumor. Mechanistically, Gal1 reprograms the tumor endothelium to upregulate cell-surface programmed death ligand 1 (PD-L1) and galectin-9. Using genetic and pharmacological approaches, we show that Gal1 blockade increases intratumoral T cell infiltration, leading to a better response to anti-PD1 therapy with or without radiotherapy. Our study reveals the function of Gal1 in transforming the tumor endothelium into an immune-suppressive barrier and that its inhibition synergizes with ICIs.

Original languageEnglish (US)
Pages (from-to)5553-5567
Number of pages15
JournalJournal of Clinical Investigation
Volume129
Issue number12
DOIs
StatePublished - Dec 2 2019

ASJC Scopus subject areas

  • Medicine(all)

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    Nambiar, D. K., Aguilera, T., Cao, H., Kwok, S., Kong, C., Bloomstein, J., Wang, Z., Rangan, V. S., Jiang, D., Von Eyben, R., Liang, R., Agarwal, S., Dimitrios Colevas, A., Korman, A., Allen, C. T., Uppaluri, R., Koong, A. C., Giaccia, A., & Le, Q. T. (2019). Galectin-1-driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance. Journal of Clinical Investigation, 129(12), 5553-5567. https://doi.org/10.1172/JCI129025