VISTA is an acidic pH-selective ligand for PSGL-1

Johnston, Robert J.; Su, Linhui Julie; Pinckney, Jason; Critton, D.A.; Boyer, E. W.; Krishnakumar, Arathi; Corbett, Martin J.; Rankin, Andrew L.; DiBella, Rose A.; Campbell, Lynne; Martin, Gaëlle H.; Lemar, Hadia; Cayton, Thomas; Huang, Richard Y.‐C.; Deng, Xiaolong; Nayeem, Akbar; Chen, Haibin; Ergel, Burce; Rizzo, Joseph M.; Yamniuk, Aaron P.; Dutta, Sanjib; Ngo, Justine; Shorts, Andrea Olga; Ramakrishnan, Radha; Kozhich, Alexander; Holloway, James L.; Fang, Huihui; Wang, Ying-Kai; Yang, Zheng; Thiam, Kader; Rakestraw, Ginger; Rajpal, Arvind; Sheppard, Paul W.; Quigley, Michael; Bahjat, Keith S.; Korman, Alan J.

doi:10.1038/s41586-019-1674-5

Cited by 251 publications

(314 citation statements)

References 46 publications

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“…First, the magnitude of T cell response was synergistically enhanced in the absence of VISTA and PD‐1 . More importantly, blockade of VISTA and PD‐1/PD‐L1 more profoundly enhances tumor immunity than targeting either pathway . This has sparked interest in VISTA as a potential target for cancer immunotherapy.…”

Section: The Promise Of Vista In Cancer Immunotherapymentioning

confidence: 99%

“…In human prostate cancer, Sharma and colleagues showed that VISTA and PD‐L1 are expressed on independent subsets of macrophages, which further suggests potential combination therapy. Importantly, VISTA combination with PD‐1 blockade engendered strong immunity to tumors resistant to either checkpoint as monotherapy . A subtle yet critical aspect for the success of immunotherapy is the timing of checkpoint blockade.…”

Section: The Promise Of Vista In Cancer Immunotherapymentioning

confidence: 99%

“…As VSIG3 expression is undetectable in the hematopoietic compartment, the in‐vivo physiological relevance of this interaction remains to be validated. Alan Korman and colleagues presented the exciting finding of a pH‐dependent interaction between VISTA and P‐selectin glycoprotein ligand‐1 (PSGL‐1) . The investigators highlight a unique property of the extracellular domain of VISTA, which is enriched in histidine residues.…”

Section: The Vista Ligand Mysterymentioning

confidence: 99%

“…The investigators highlight a unique property of the extracellular domain of VISTA, which is enriched in histidine residues. The side chain of histidine becomes deprotonated at acidic pH conditions, such as those found within the TME, and this post‐translational modification permits binding to PSGL‐1 . The importance of this post‐translational modification in dictating VISTA ligand interactions cannot be understated, given that VISTA multimers (including VISTA–Fc) only bind leukocytes under acidic conditions.…”

Section: The Vista Ligand Mysterymentioning

confidence: 99%

“…On naive T cells, underglycosylated PSGL‐1 is a receptor for the chemokine CCL21 and competes with CCR7 in binding CCL19, suggesting an important role for regulation of naive T cell trafficking . Moreover, the binding of VISTA requires tyrosine sulfation of PSGL‐1 .…”

Section: The Vista Ligand Mysterymentioning

confidence: 99%

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VISTA: Coming of age as a multi-lineage immune checkpoint

ElTanbouly

Schaafsma

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et al. 2020

Clinical and Experimental Immunology

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The immune response is governed by a highly complex set of interactions among cells and mediators. T cells may be rendered dysfunctional by the presence of high levels of antigen in the absence of co-stimulation while myeloid cells may be programmed towards an immunosuppressive state that promotes cancer growth and metastasis while deterring tumor immunity. In addition, inhibitory programs driven by immune checkpoint regulators dampen anti-tumor immunity. The ideal cancer immunotherapy treatment will improve both cross-priming in the tumor microenvironment and relieve suppression by the inhibitory checkpoints. Recently, blockade of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) has elicited impressive results, but not in all patients, so additional targets are under investigation. V-set immunoglobulin domain suppressor of T cell activation (VISTA) is a novel immunoregulatory receptor that is broadly expressed on cells of the myeloid and lymphoid lineages, and is frequently implicated as a poor prognostic indicator in multiple cancers. Importantly, antibody targeting of VISTA uniquely engages both innate and adaptive immunity. This, combined with the expression of VISTA and its non-redundant activities compared to other immune checkpoint regulators, qualifies VISTA to be a promising target for improving cancer immunotherapy.

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Section: The Promise Of Vista In Cancer Immunotherapymentioning

confidence: 99%

Section: The Promise Of Vista In Cancer Immunotherapymentioning

confidence: 99%

Section: The Vista Ligand Mysterymentioning

confidence: 99%

Section: The Vista Ligand Mysterymentioning

confidence: 99%

Section: The Vista Ligand Mysterymentioning

confidence: 99%

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VISTA: Coming of age as a multi-lineage immune checkpoint

ElTanbouly

Schaafsma

Noelle

et al. 2020

Clinical and Experimental Immunology

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Cancer Immunotherapy

Sharma¹,

Anandhan²,

Siddiqui³

et al. 2022

Holland‐Frei Cancer Medicine

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Overview The basic principles that guide cancer immunology are immune surveillance, immune editing, and immune tolerance. Rapid increase in the knowledge of mechanistic details of these basic principles has led to clinical success in the treatment of cancer. In this article, we discuss the basic principles and recent advances in the field of basic and clinical immunotherapy that has given credence to the long‐held belief that the immune system can be used to treat cancer. Further, we also focus on the challenges associated with immunotherapies in the clinic, the role of combining different types of immunotherapies and other therapeutic modalities in the treatment of cancer.

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Targeted Anti‐Tumor Immunotherapy Using Tumor Infiltrating Cells

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Zhang

et al. 2021

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In the tumor microenvironment, T cells, B cells, and many other cells play important and distinct roles in anti-tumor immunotherapy. Although the immune checkpoint blockade and adoptive cell transfer can elicit durable clinical responses, only a few patients benefit from these therapies. Increased understanding of tumor-infiltrating immune cells can provide novel therapies and drugs that induce a highly specific anti-tumor immune response to certain groups of patients. Herein, the recent research progress on tumor-infiltrating B cells and T cells, including CD8 + T cells, CD4 + T cells, and exhausted T cells and their role in anti-tumor immunity, is summarized. Moreover, several anti-tumor therapy approaches are discussed based on different immune cells and their prospects for future applications in cancer treatment.

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VISTA is an acidic pH-selective ligand for PSGL-1

Cited by 251 publications

References 46 publications

VISTA: Coming of age as a multi-lineage immune checkpoint

VISTA: Coming of age as a multi-lineage immune checkpoint

Cancer Immunotherapy

Targeted Anti‐Tumor Immunotherapy Using Tumor Infiltrating Cells

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