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Updated: May 26, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
PD-1H (VISTA) Expression in Cutaneous Squamous Cell Carcinoma Is Correlated with T-Cell Infiltration and Activation
Michal Kidacki1, Christina Cho2, Francesc Lopez-Giraldez3
1Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA.
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.
Insights
VISTA, an immune checkpoint, is expressed in nearly half of cutaneous squamous cell carcinoma (cSCC) tumors. High VISTA expression correlates with increased T-cell activity, suggesting it as a potential immunotherapy target for cSCC.
Area of Science:
- Immunology
- Oncology
- Dermatology
Background:
- Cutaneous squamous cell carcinoma (cSCC) is a common cancer with a significant mortality rate.
- Current immunotherapies targeting PD-1/PD-L1 are effective in only half of cSCC patients.
- The immune inhibitory receptor VISTA (PD-1H) is a potential therapeutic target in cancer.
Purpose of the Study:
- To investigate VISTA expression in cSCC tissues.
- To correlate VISTA expression with PD-L1 expression and T-cell infiltration/activation.
- To evaluate VISTA as a potential therapeutic target in cSCC immunotherapy.
Main Methods:
- Multiplexed quantitative immunofluorescence was used on 76 primary cSCC tissues.
- VISTA and PD-L1 expression levels were quantified.
- T-cell infiltration and activation were assessed using Ki-67 and granzyme B markers.
Main Results:
- VISTA was expressed in 48% of cSCCs, and PD-L1 in 58%.
- High VISTA expression, not PD-L1, correlated with increased T-cell infiltration and activation (Ki-67, granzyme B).
- No significant correlation was found between VISTA and PD-L1 coexpression, indicating distinct tumor microenvironments.
Conclusions:
- VISTA is frequently expressed in cSCC and is associated with a more inflamed tumor microenvironment.
- VISTA expression patterns differ from PD-L1, suggesting it represents a distinct immunosuppressive pathway.
- Targeting VISTA may offer a novel immunotherapy strategy for cSCC patients unresponsive to PD-1/PD-L1 blockade.
