Tumor-resident regulatory T cells in pancreatic cancer express the αvβ5 integrin as a targetable activation marker

Suzuki, K.; Kunisada, Y.; Miyamura, N.; Eikawa, S.; Hurtado de Mendoza, T.; Mose, E. S.; Lu, C.; Kuroda, Y.; Ruoslahti, E.; Lowy, A. M.; Sugahara, K. N.

doi:10.1101/2023.05.24.542137

bioRxiv · 10.1101/2023.05.24.542137

Tumor-resident regulatory T cells in pancreatic cancer express the αvβ5 integrin as a targetable activation marker

Suzuki, K.·Kunisada, Y.·Miyamura, N.·Eikawa, S.·Hurtado de Mendoza, T.·Mose, E. S.·Lu, C.·Kuroda, Y.·Ruoslahti, E.·Lowy, A. M.·Sugahara, K. N.

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) has abundant immunosuppressive regulatory T cells (Tregs), which contribute to a microenvironment resistant to immunotherapy. Here, we report that Tregs in the PDAC tissue, but not those in the spleen, express the v{beta}5 integrin in addition to neuropilin-1 (NRP-1), which makes them susceptible to the iRGD tumor-penetrating peptide, which targets cells positive for v integrin- and NRP-1. As a result, long-term treatment of PDAC mice with iRGD leads to tumor-specific depletion of Tregs and improved efficacy of immune checkpoint blockade. v{beta}5 integrin+ Tregs are induced from both naive CD4+ T cells and natural Tregs upon T cell receptor stimulation, and represent a highly immunosuppressive subpopulation of CCR8+ Tregs. This study identifies the v{beta}5 integrin as a marker for activated tumor-resident Tregs, which can be targeted to achieve tumor-specific Treg depletion and thereby augment anti-tumor immunity for PDAC therapy.

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Suzuki, K., Kunisada, Y., Miyamura, N., Eikawa, S., Hurtado de Mendoza, T., Mose, E. S., Lu, C., Kuroda, Y., Ruoslahti, E., Lowy, A. M., Sugahara, K. N.. 2023-05-24. Tumor-resident regulatory T cells in pancreatic cancer express the αvβ5 integrin as a targetable activation marker. https://doi.org/10.1101/2023.05.24.542137

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