PD-1H (VISTA) Expression in Cutaneous Squamous Cell Carcinoma Is Correlated with T-Cell Infiltration and Activation

Michal Kidacki; Christina Cho; Francesc Lopez-Giraldez; Baozhu Huang; Jianwei He; Patricia Gaule; Lieping Chen; Matthew D. Vesely

doi:10.1016/j.jid.2025.01.030

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PD-1H (VISTA) Expression in Cutaneous Squamous Cell Carcinoma Is Correlated with T-Cell Infiltration and Activation

Journal article

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PD-1H (VISTA) Expression in Cutaneous Squamous Cell Carcinoma Is Correlated with T-Cell Infiltration and Activation

Michal Kidacki, Christina Cho, Francesc Lopez-Giraldez, Baozhu Huang, Jianwei He, Patricia Gaule, Lieping Chen and Matthew D. Vesely

Journal of investigative dermatology, Vol.145(9), pp.2313-2324.e6

09/01/2025

DOI: 10.1016/j.jid.2025.01.030

PMCID: PMC12353361

PMID: 39983979

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12353361/View

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Abstract

Cutaneous squamous cell carcinoma (cSCC) is one of the most common human cancers, with an estimated death rate approaching or exceeding that of melanoma. Immune inhibitory receptor antagonism through the blockade of PD-1 or its ligand, PD-L1, has revolutionized the treatment of cSCC; however, approximately half of patients still fail to respond. The inhibitory receptor PD-1H (also known as VISTA) controls T-cell and myeloid cell functions in preclinical cancer studies. Currently, cancer clinical trials using anti–VISTA-blocking antibodies are ongoing. We sought to determine the extent of VISTA expression in cSCCs and to correlate its expression with PD-L1 expression. Using multiplexed quantitative immunofluorescence of primary cSCC tissues (n = 76), we found that VISTA was expressed in 48% of cSCCs and that PD-L1 was expressed in 58% of cSCCs. We found that high VISTA expression, more than PD-L1 expression, correlated with greater T-cell infiltration and activation, as measured by the proliferation marker Ki-67 and the cytotoxic marker granzyme B. Furthermore, there was no significant correlation between VISTA and PD-L1 coexpression within the same cSCCs, suggesting that individual tumors have distinct immunosuppressive microenvironments. These findings provide a rationale for the targeting of VISTA in cSCC immunotherapy.

Cancer immunotherapy

Cutaneous squamous cell carcinoma

PD-1H

VISTA

Details

Title: Subtitle: PD-1H (VISTA) Expression in Cutaneous Squamous Cell Carcinoma Is Correlated with T-Cell Infiltration and Activation
Creators: Michal Kidacki - Yale University
Christina Cho - Yale University
Francesc Lopez-Giraldez - Yale School of Medicine
Baozhu Huang - Yale University
Jianwei He - Yale University
Patricia Gaule - Yale University
Lieping Chen - Yale University
Matthew D. Vesely - Yale University
Resource Type: Journal article
Publication Details: Journal of investigative dermatology, Vol.145(9), pp.2313-2324.e6
DOI: 10.1016/j.jid.2025.01.030
PMID: 39983979
PMCID: PMC12353361
NLM abbreviation: J Invest Dermatol
ISSN: 0022-202X
eISSN: 1523-1747
Publisher: Elsevier Inc
Grant note: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: K08AR080777 National Cancer Institute at the National Institutes of Health: R50CA265359
ACKNOWLEDGMENTS MK was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number T32AR001016. MDV was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number K08AR080777. FLG was supported by the National Cancer Institute at the National Institutes of Health under award number R50CA265359.
Language: English
Date published: 09/01/2025
Academic Unit: Dermatology; Internal Medicine
Record Identifier: 9984949511102771

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