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. 2017 Apr 12:10:2147-2154.
doi: 10.2147/OTT.S128451. eCollection 2017.

Soluble cytotoxic T-lymphocyte antigen 4: a favorable predictor in malignant tumors after therapy

Qiqi Liu  1 , Pingping Hu  1 , Guodong Deng  1 , Jingxin Zhang  2 , Ning Liang  1 , Jian Xie  1 , Lili Qiao  3 , Hui Luo  4 , Jiandong Zhang  1
Affiliations

Soluble cytotoxic T-lymphocyte antigen 4: a favorable predictor in malignant tumors after therapy

Qiqi Liu et al. Onco Targets Ther. .

Abstract

Purpose: Soluble cytotoxic T-lymphocyte antigen 4 (sCTLA-4), one of the isoforms of CTLA-4, was discovered to be critical in downregulating the negative signal of CTLA-4 in T-cell responses. Contrary to the classical immunosuppressive effect of CTLA-4, its immunoregulatory function might be complicated. However, the clinical significance of sCTLA-4 to immune regulation and the variation in cancer therapy have not been elucidated. We postulated that the level of sCTLA-4 might affect the outcome of cancer prognosis.

Patients and methods: Serum concentrations of sCTLA-4 before and after therapy in 141 locally advanced and advanced cancer patients were measured and survival analyses was performed. Hazard ratio and 95% confidence interval for overall survival (OS) were calculated. Cutoffs were determined by median across the sCTLA-4 level of entire patients.

Results: High expression of sCTLA-4 after therapy indicated significant longer OS and progression-free survival (PFS) (all P<0.01). Among all subgroups, sCTLA-4 levels after therapies were found to be significantly higher than that of 1 day before, which was also negatively correlated with tumor node metastasis stage and lymph node metastasis (all P<0.05). Multivariate analysis revealed that sCTLA-4 level was a strong independent prognostic factor for OS and PFS (all P<0.05).

Conclusion: Our data demonstrated the favorable prognostic significance of sCTLA-4 and may lead to the development of new immunotherapy options for cancer patients.

Keywords: cancer prognosis; cancer therapy; immunotherapy; soluble cytotoxic T-lymphocyte antigen 4; survival.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Level of sCTLA-4 in all 4 groups. Notes: Compared with the level of sCTLA-4 1 day before therapies, sCTLA-4 levels during therapies were significantly higher among all these 4 subgroups including the (A) RT, (B) chemotherapy, (C) CRT, and (D) whole patient group (all P<0.05). Abbreviations: CRT, chemoradiotherapy; RT, radiotherapy; sCTLA-4, soluble cytotoxic T-lymphocyte antigen 4.
Figure 2
Figure 2
Survival curves for OS in all 4 groups. Notes: Survival analysis was according to sCTLA-4 levels during therapy, with green indicating upregulated sCTLA-4 levels and blue denoting downregulated sCTLA-4 levels. Patients in the (A) RT, (B) chemotherapy, (C) CRT, and (D) whole patient groups with upregulated sCTLA-4 levels had longer OS than patients with downregulated sCTLA-4 levels (all P<0.05, log-rank test). Abbreviations: CRT, chemoradiotherapy; OS, overall survival; RT, radiotherapy; sCTLA-4, soluble cytotoxic T-lymphocyte antigen 4.
Figure 3
Figure 3
Survival curves for PFS in all 4 groups. Notes: Survival analysis was according to sCTLA-4 levels during therapy, with green indicating upregulated sCTLA-4 levels and blue denoting downregulated sCTLA-4 levels. Patients in the (A) RT, (B) chemotherapy, (C) CRT, and (D) whole patient groups with upregulated sCTLA-4 levels had longer PFS than patients with downregulated sCTLA-4 levels (all P<0.05, log-rank test). Abbreviations: CRT, chemoradiotherapy; PFS, progression-free survival; RT, radiotherapy; sCTLA-4, soluble cytotoxic T-lymphocyte antigen 4.
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