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

Liao,Hong; Zhu,Hongmei; Liu,Shanling; Wang,He

doi:10.3892/ol.2018.9059

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

Authors:
- Hong Liao
- Hongmei Zhu
- Shanling Liu
- He Wang
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Affiliations: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: July 2, 2018 https://doi.org/10.3892/ol.2018.9059
Pages: 3465-3472
Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

V‑domain immunoglobulin suppressor of T cell activation (VISTA) is a novel negative immune checkpoint that belongs to the B7 family. VISTA is primarily expressed on hematopoietic cells and inhibits T cell proliferation and cytokine production. The blockade of VISTA has demonstrated promising results in certain murine tumor models. In the present study, an immunohistochemical analysis of VISTA expression on tumor cells, intratumoral immune cells and vascular endothelial cells was performed in a cohort of 65 patients with ovarian cancer (OC). The associations between VISTA expression and different clinicopathological characteristics were evaluated using Fisher's exact test, and the analysis of overall survival in different groups was performed by the construction of Kaplan‑Meier curves. The results indicated that high expression of VISTA on tumor cells or ICs was significantly associated with advanced tumor stage and the presence of lymph node metastasis (LNM). However, the percentage of cases with high expression of VISTA on tumor cells (24.6%) was decreased compared with those with high expression on ICs (44.6%). There was no association between VISTA expression and the 5‑year overall survival rate, and advanced‑stage disease was the only independent predictor of poor prognosis based on multivariate Cox regression analysis. In general, VISTA expression increased with advanced disease stage and LNM, indicating that VISTA expression is involved in the progression of OC. More importantly, these data implicate VISTA as a candidate immunotherapeutic target in OC.

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1	Erickson BK, Conner MG and Landen CN Jr: The role of the fallopian tube in the origin of ovarian cancer. Am J Obstet Gynecol. 209:409–414. 2013. View Article : Google Scholar : PubMed/NCBI
2	Kurman RJ and Shih IM: The origin and pathogenesis of epithelial ovarian cancer: A proposed unifying theory. Am J Surg Pathol. 34:433–443. 2010. View Article : Google Scholar : PubMed/NCBI
3	Prat J: New insights into ovarian cancer pathology. Ann Oncol. 23 Suppl 10:x111–x117. 2012. View Article : Google Scholar : PubMed/NCBI
4	Eltabbakh GH and Awtrey CS: Current treatment for ovarian cancer. Expert Opin Pharmacother. 2:109–124. 2001. View Article : Google Scholar : PubMed/NCBI
5	Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, et al: SEER Cancer Statistics Review, 1975–2015. National Cancer Institute; Bethesda, MD: 2018, https://seer.cancer.gov/csr/1975_2015/April. 2018
6	Komiyama S, Katabuchi H, Mikami M, Nagase S, Okamoto A, Ito K, Morishige K, Suzuki N, Kaneuchi M, Yaegashi N, et al: Japan society of gynecologic oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer. Int J Clin Oncol. 21:435–446. 2016. View Article : Google Scholar : PubMed/NCBI
7	Kigawa J: New strategy for overcoming resistance to chemotherapy of ovarian cancer. Yonago Acta Med. 56:43–50. 2013.PubMed/NCBI
8	Kandalaft LE, Powell DJ Jr, Singh N and Coukos G: Immunotherapy for ovarian cancer: What's next? J Clin Oncol. 29:925–933. 2011. View Article : Google Scholar : PubMed/NCBI
9	Wang RF and Wang HY: Immune targets and neoantigens for cancer immunotherapy and precision medicine. Cell Res. 27:11–37. 2017. View Article : Google Scholar : PubMed/NCBI
10	Drerup JM, Liu Y, Padron AS, Murthy K, Hurez V, Zhang B and Curiel TJ: Immunotherapy for ovarian cancer. Curr Treat Options Oncol. 16:3172015. View Article : Google Scholar : PubMed/NCBI
11	Chen L and Han X: Anti-PD-1/PD-L1 therapy of human cancer: Past, present, and future. J Clin Invest. 125:3384–3391. 2015. View Article : Google Scholar : PubMed/NCBI
12	Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, Lu LF, Gondek D, Wang Y, Fava RA, et al: VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J Exp Med. 208:577–592. 2011. View Article : Google Scholar : PubMed/NCBI
13	Lines JL, Sempere LF, Broughton T, Wang L and Noelle R: VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy. Cancer Immunol Res. 2:510–517. 2014. View Article : Google Scholar : PubMed/NCBI
14	Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O'Connell S, Ceeraz S, Suriawinata AA, Yan S, Ernstoff MS and Noelle R: VISTA is an immune checkpoint molecule for human T cells. Cancer Res. 74:1924–1932. 2014. View Article : Google Scholar : PubMed/NCBI
15	Deng J, Le Mercier I, Kuta A and Noelle RJ: A New VISTA on combination therapy for negative checkpoint regulator blockade. J Immunother Cancer. 4:862016. View Article : Google Scholar : PubMed/NCBI
16	Okudaira K, Hokari R, Tsuzuki Y, Okada Y, Komoto S, Watanabe C, Kurihara C, Kawaguchi A, Nagao S, Azuma M, et al: Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model. Int J Oncol. 35:741–749. 2009.PubMed/NCBI
17	Hu Q, Peng J, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Liu S and Wang H: Lin28B is a novel prognostic marker in gastric adenocarcinoma. Int J Clin Exp Pathol. 7:5083–5092. 2014.PubMed/NCBI
18	Wang Q, Li J, Li G, Li Y, Xu C, Li M, Xu G and Fu S: Prognostic significance of sphingosine kinase 2 expression in non-small cell lung cancer. Tumour Biol. 35:363–368. 2014. View Article : Google Scholar : PubMed/NCBI
19	Böger C, Behrens HM, Krüger S and Röcken C: The novel negative checkpoint regulator VISTA is expressed in gastric carcinoma and associated with PD-L1/PD-1: A future perspective for a combined gastric cancer therapy? Oncoimmunology. 6:e12932152017. View Article : Google Scholar : PubMed/NCBI
20	Wu L, Deng WW, Huang CF, Bu LL, Yu GT, Mao L, Zhang WF, Liu B and Sun ZJ: Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma. Cancer Immunol Immunother. 66:627–636. 2017. View Article : Google Scholar : PubMed/NCBI
21	Pardoll DM: The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 12:252–264. 2012. View Article : Google Scholar : PubMed/NCBI
22	Ni L and Dong C: New checkpoints in cancer immunotherapy. Immunol Rev. 276:52–65. 2017. View Article : Google Scholar : PubMed/NCBI
23	Le Mercier I, Chen W, Lines JL, Day M, Li J, Sergent P, Noelle RJ and Wang L: VISTA regulates the development of protective antitumor immunity. Cancer Res. 74:1933–1944. 2014. View Article : Google Scholar : PubMed/NCBI
24	Nicklin JL, McGrath S, Tripcony L, Garrett A, Land R, Tang A, Perrin L, Chetty N, Jagasia N, Crandon AJ, et al: The shift toward neo-adjuvant chemotherapy and interval debulking surgery for management of advanced ovarian and related cancers in a population-based setting: Impact on clinical outcomes. Aust N Z J Obstet Gynaecol. 57:651–658. 2017. View Article : Google Scholar : PubMed/NCBI
25	Hu Q, Peng J, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Liu S and Wang H: Elevated cleaved caspase-3 is associated with shortened overall survival in several cancer types. Int J Clin Exp Pathol. 7:5057–5070. 2014.PubMed/NCBI
26	Webb JR, Milne K, Kroeger DR and Nelson BH: PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer. Gynecol Oncol. 141:293–302. 2016. View Article : Google Scholar : PubMed/NCBI
27	Markman M: Immunotherapy in ovarian cancer-where are we going? Am J Hematol Oncol. 12:2016.
28	Kandalaft LE, Motz GT, Duraiswamy J and Coukos G: Tumor immune surveillance and ovarian cancer: Lessons on immune mediated tumor rejection or tolerance. Cancer Metastasis Rev. 30:141–151. 2011. View Article : Google Scholar : PubMed/NCBI
29	De Felice F, Marchetti C, Palaia I, Musio D, Muzii L, Tombolini V and Panici PB: Immunotherapy of ovarian cancer: The role of checkpoint inhibitors. J Immunol Res. 2015:1918322015. View Article : Google Scholar : PubMed/NCBI