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Opening up new VISTAs: V-domain immunoglobulin suppressor of T cell activation (VISTA) targeted near-infrared photoimmunotherapy (NIR-PIT) for enhancing host immunity against cancers

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Abstract

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an inhibitory immune checkpoint molecule that is broadly expressed on lymphoid and myeloid cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Near-infrared photoimmunotherapy (NIR-PIT) is a cancer treatment that utilizes an antibody-photoabsorber (IRDye 700DX NHS ester) conjugate to selectively kill target cells after the local application of NIR light. Depletion of VISTA-expressing cells in the tumor microenvironment (TME) using NIR-PIT could enhance anti-tumor immune responses by removing immune suppressive cells. The purpose of this study was to evaluate the anti-tumor efficacy of VISTA-targeted NIR-PIT using two murine tumor models, MC38-luc and LL2-luc. VISTA was expressed on T cells including Tregs and MDSCs in the TME of these tumors. In contrast, CD45 − cells, including cancer cells, did not express VISTA. VISTA-targeted NIR-PIT depleted VISTA-expressing cells ex vivo. In vivo VISTA-targeted NIR-PIT inhibited tumor progression and prolonged survival in both models. After VISTA-targeted NIR-PIT, augmented CD8 + T cell and dendritic cell activation were observed in regional lymph nodes. In conclusion, VISTA-targeted NIR-PIT can effectively treat tumors by decreasing VISTA-expressing immune suppressor cells in the TME. Local depletion of VISTA-expressing cells in the tumor bed using NIR-PIT is a promising new cancer immunotherapy for treating various types of tumors.

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Funding

This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (ZIA BC 011513). FI was also supported with a Grant from National Center for Global Health and Medicine Research Institute, Tokyo, Japan.

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Authors and Affiliations

  1. Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA

    Hiroaki Wakiyama, Aki Furusawa, Ryuhei Okada, Fuyuki Inagaki, Takuya Kato, Hideyuki Furumoto, Hiroshi Fukushima, Shuhei Okuyama, Peter L. Choyke & Hisataka Kobayashi

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  1. Hiroaki Wakiyama
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  2. Aki Furusawa
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  3. Ryuhei Okada
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  4. Fuyuki Inagaki
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  6. Hideyuki Furumoto
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  10. Hisataka Kobayashi
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Correspondence to Hisataka Kobayashi.

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Wakiyama, H., Furusawa, A., Okada, R. et al. Opening up new VISTAs: V-domain immunoglobulin suppressor of T cell activation (VISTA) targeted near-infrared photoimmunotherapy (NIR-PIT) for enhancing host immunity against cancers. Cancer Immunol Immunother 71, 2869–2879 (2022). https://doi.org/10.1007/s00262-022-03205-5

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