High-expression of V-domain Imuunoglobulin Suppressor of T-cell Activation (VISTA) Is Correlated with Advanced Pathological Features in Patients with Pancreatic Ductal Adenocarcinoma
-
Hamid Nickho
,
Reza Falak
,
Fereshteh Rezagholizadeh
,
Majid Khoshmirsafa
,
Mohammad Taghi Joghataei
,
Shabnam Mollazadeh Ghomi
,
Elaheh Safari
Abstract
V-domain Imuunoglobulin suppressor of T-cell activation (VISTA) seems a promising immune checkpoint target in cancer treatment; however, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains unknown.
Herein, 29 fresh PDAC tissue samples were used to evaluate the mRNA expression level of VISTA by real-time polymerase chain reaction (PCR). Besides, 40 formalin-fixed paraffin-embedded PDAC tissues were collected to evaluate VISTA protein expression by immunohistochemistry.
Real-time PCR indicated that high expression of VISTA was significantly correlated with advanced stages of the cancer, based on the tumor/node/metastasis (TNM) stagingand tumor cell differentiation. Immunohistochemistry results also showed significant correlation of the elevated cytoplasmic expression of VISTA with advanced TNM stages, older age of the patients and was a worsening indicator, regarding the disease-specific survival.
In conclusion, we found that the expression levels of VISTA can be a potential prognostic biomarker in PDAC patients and its elevated levels are correlated with poor prognostic outcomes.
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14. Zhang M, Pang H-J, Zhao W, Li Y-F, Yan L-X, Dong Z-Y, et al. VISTA expression associated with CD8 confers a favorable immune microenvironment and better overall survival in hepatocellular carcinoma. BMC Cancer. 2018;18:1-8.
15. Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, et al. VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J Exp Med. 2011;208(3):577-92.
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17. Yuan L, Tatineni J, Mahoney KM, Freeman GJ. VISTA: a mediator of quiescence and a promising target in cancer immunotherapy. Trends Immunol. 2021;42(3):209-27.
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21. Liu C-Y, Xu J-Y, Shi X-Y, Huang W, Ruan T-Y, Xie P, et al. M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab Invest. 2013;93(7):844-54.
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25. Ganesan N, Akshaya Devi B. In Silico Molecular Docking Analysis of Plant Compounds Against VISTA Protein: A Novel Target in Cancer.
26. Wasif N, Ko CY, Farrell J, Wainberg Z, Hines OJ, Reber H, et al. Impact of tumor grade on prognosis in pancreatic cancer: should we include grade in AJCC staging? Ann Surg Oncol. 2010;17:2312-20.
27. Hartwig W, Hackert T, Hinz U, Gluth A, Bergmann F, Strobel O, et al. Pancreatic cancer surgery in the new millennium: better prediction of outcome. Ann Surg Oncol. 2011;254(2):311-9.
28. Robbins SL, Cotran RS, Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran pathologic basis of disease. Robbins and Cotran pathologic basis of disease2010. p. 1450-.
29. Dbouk M, Katona BW, Brand RE, Chak A, Syngal S, Farrell JJ, et al. The multicenter cancer of pancreas screening study: impact on stage and survival. J Clin Oncol. 2022;40(28):3257.
30. Liao H, Zhu H, Liu S, Wang H. Expression of V‑domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer. Oncol Lett. 2018;16(3):3465-72.
31. Zong L, Mo S, Sun Z, Lu Z, Yu S, Chen J, et al. Analysis of the immune checkpoint V-domain Ig-containing suppressor of T-cell activation (VISTA) in endometrial cancer. Mod Pathol. 2022;35(2):266-73.
32. Rabadi D, Sajani AA, Noelle RJ, Lines JL. The role of VISTA in the tumor microenvironment. J Cancer Metastasis Treat. 2022;8:24.
33. Le Mercier I, Chen W, Lines JL, Day M, Li J, Sergent P, et al. VISTA regulates the development of protective antitumor immunity. Cancer Res. 2014;74(7):1933-44.
34. Wang J, Wu G, Manick B, Hernandez V, Renelt M, Erickson C, et al. VSIG‐3 as a ligand of VISTA inhibits human T‐cell function. Immunology. 2019;156(1):74-85.
35. Johnston RJ, Su LJ, Pinckney J, Critton D, Boyer E, Krishnakumar A, et al. VISTA is an acidic pH-selective ligand for PSGL-1. Nature. 2019;574(7779):565-70.
36. Loeser H, Kraemer M, Gebauer F, Bruns C, Schröder W, Zander T, et al. The expression of the immune checkpoint regulator VISTA correlates with improved overall survival in pT1/2 tumor stages in esophageal adenocarcinoma. Oncoimmunology. 2019;8(5):e1581546.
2. Chandana S, Babiker HM, Mahadevan D. Therapeutic trends in pancreatic ductal adenocarcinoma (PDAC). Expert Opin Investig Drugs. 2019;28(2):161-77.
3. Hou Z, Pan Y, Fei Q, Lin Y, Zhou Y, Liu Y, et al. Prognostic significance and therapeutic potential of the immune checkpoint VISTA in pancreatic cancer. J Cancer Res Clin Oncol. 2021;147:517-31.
4. Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010;33(8):828.
5. Farhangnia P, Ghomi SM, Mollazadehghomi S, Nickho H, Akbarpour M, Delbandi A-A. SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy. Front immunol. 2023;14:1174138.
6. Feng M, Xiong G, Cao Z, Yang G, Zheng S, Song X, et al. PD-1/PD-L1 and immunotherapy for pancreatic cancer. Cancer Lett. 2017;407:57-65.
7. ElTanbouly M, Schaafsma E, Noelle R, Lines J. VISTA: Coming of age as a multi-lineage immune checkpoint. Clin Exp Immunol. 2020;200(2):120-30.
8. ElTanbouly MA, Zhao Y, Nowak E, Li J, Schaafsma E, Le Mercier I, et al. VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance. Science. 2020;367(6475):eaay0524.
9. Blando J, Sharma A, Higa MG, Zhao H, Vence L, Yadav SS, et al. Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer. PNAS. 2019;116(5):1692-7.
10. Habtezion A, Edderkaoui M, Pandol SJ. Macrophages and pancreatic ductal adenocarcinoma. Cancer Lett. 2016;381(1):211-6.
11. Xie X, Zhang J, Shi Z, Liu W, Hu X, Qie C, et al. The expression pattern and clinical significance of the immune checkpoint regulator VISTA in human breast cancer. Front immunol. 2020;11:563044.
12. Bailey P, Chang DK, Nones K, Johns AL, Patch A-M, Gingras M-C, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47-52.
13. Carstens JL, Correa de Sampaio P, Yang D, Barua S, Wang H, Rao A, et al. Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer. Nat Commun. 2017;8(1):15095.
14. Zhang M, Pang H-J, Zhao W, Li Y-F, Yan L-X, Dong Z-Y, et al. VISTA expression associated with CD8 confers a favorable immune microenvironment and better overall survival in hepatocellular carcinoma. BMC Cancer. 2018;18:1-8.
15. Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, et al. VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J Exp Med. 2011;208(3):577-92.
16. Loch FN, Kamphues C, Beyer K, Schineis C, Rayya W, Lauscher JC, et al. The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma. Int J Mol Sci. 2023;24(3):2160.
17. Yuan L, Tatineni J, Mahoney KM, Freeman GJ. VISTA: a mediator of quiescence and a promising target in cancer immunotherapy. Trends Immunol. 2021;42(3):209-27.
18. Xu W, Hiếu T, Malarkannan S, Wang L. The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cell Mol Immunol. 2018;15(5):438-46.
19. Esparvarinha M, Madadi S, Aslanian‐Kalkhoran L, Nickho H, Dolati S, Pia H, et al. Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints. Cell Biol Int. 2023;47(3):507-19.
20. Deng J, Li J, Sarde A, Lines JL, Lee Y-C, Qian DC, et al. Hypoxia-induced VISTA promotes the suppressive function of myeloid-derived suppressor cells in the tumor microenvironment. Cancer Immunol Res. 2019;7(7):1079-90.
21. Liu C-Y, Xu J-Y, Shi X-Y, Huang W, Ruan T-Y, Xie P, et al. M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab Invest. 2013;93(7):844-54.
22. Jin J, Lin J, Xu A, Lou J, Qian C, Li X, et al. CCL2: an important mediator between tumor cells and host cells in tumor microenvironment. Front Oncol. 2021;11:722916.
23. Mulati K, Hamanishi J, Matsumura N, Chamoto K, Mise N, Abiko K, et al. VISTA expressed in tumour cells regulates T cell function. Br J Cancer. 2019;120(1):115-27.
24. Wu C, Cao X, Zhang X. VISTA inhibitors in cancer immunotherapy: a short perspective on recent progresses. RSC med chem. 2021;12(10):1672-9.
25. Ganesan N, Akshaya Devi B. In Silico Molecular Docking Analysis of Plant Compounds Against VISTA Protein: A Novel Target in Cancer.
26. Wasif N, Ko CY, Farrell J, Wainberg Z, Hines OJ, Reber H, et al. Impact of tumor grade on prognosis in pancreatic cancer: should we include grade in AJCC staging? Ann Surg Oncol. 2010;17:2312-20.
27. Hartwig W, Hackert T, Hinz U, Gluth A, Bergmann F, Strobel O, et al. Pancreatic cancer surgery in the new millennium: better prediction of outcome. Ann Surg Oncol. 2011;254(2):311-9.
28. Robbins SL, Cotran RS, Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran pathologic basis of disease. Robbins and Cotran pathologic basis of disease2010. p. 1450-.
29. Dbouk M, Katona BW, Brand RE, Chak A, Syngal S, Farrell JJ, et al. The multicenter cancer of pancreas screening study: impact on stage and survival. J Clin Oncol. 2022;40(28):3257.
30. Liao H, Zhu H, Liu S, Wang H. Expression of V‑domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer. Oncol Lett. 2018;16(3):3465-72.
31. Zong L, Mo S, Sun Z, Lu Z, Yu S, Chen J, et al. Analysis of the immune checkpoint V-domain Ig-containing suppressor of T-cell activation (VISTA) in endometrial cancer. Mod Pathol. 2022;35(2):266-73.
32. Rabadi D, Sajani AA, Noelle RJ, Lines JL. The role of VISTA in the tumor microenvironment. J Cancer Metastasis Treat. 2022;8:24.
33. Le Mercier I, Chen W, Lines JL, Day M, Li J, Sergent P, et al. VISTA regulates the development of protective antitumor immunity. Cancer Res. 2014;74(7):1933-44.
34. Wang J, Wu G, Manick B, Hernandez V, Renelt M, Erickson C, et al. VSIG‐3 as a ligand of VISTA inhibits human T‐cell function. Immunology. 2019;156(1):74-85.
35. Johnston RJ, Su LJ, Pinckney J, Critton D, Boyer E, Krishnakumar A, et al. VISTA is an acidic pH-selective ligand for PSGL-1. Nature. 2019;574(7779):565-70.
36. Loeser H, Kraemer M, Gebauer F, Bruns C, Schröder W, Zander T, et al. The expression of the immune checkpoint regulator VISTA correlates with improved overall survival in pT1/2 tumor stages in esophageal adenocarcinoma. Oncoimmunology. 2019;8(5):e1581546.
| Files | ||
| Issue | Vol 23 No 3 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i3.15636 | |
| Keywords | ||
| Immune checkpoint Pancreatic cancer Pancreatic ductal adenocarcinoma V-domain immunoglobulin suppressor of T cell activation | ||
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How to Cite
1.
Nickho H, Falak R, Rezagholizadeh F, Khoshmirsafa M, Joghataei MT, Mollazadeh Ghomi S, Safari E. High-expression of V-domain Imuunoglobulin Suppressor of T-cell Activation (VISTA) Is Correlated with Advanced Pathological Features in Patients with Pancreatic Ductal Adenocarcinoma. Iran J Allergy Asthma Immunol. 2024;23(3):257-271.
