The expression of the immune checkpoint regulator VISTA correlates with improved overall survival in pT1/2 tumor stages in esophageal adenocarcinoma

Abstract

Immune checkpoint modulation in cancer has been demonstrated as a high-value therapeutic strategy in many tumor entities. VISTA is an immune checkpoint receptor regulating T-cell function. To the best of our knowledge, nothing is known about the expression and prognostic impact of VISTA on tumor infiltrating lymphocytes (TILs) in the tumor microenvironment of esophageal adenocarcinoma (EAC). We analyzed in total 393 EACs within a test-cohort (n = 165) and a validation-cohort (n = 228) using a monoclonal antibody (clone D1L2G). These data were statistically correlated with clinical as well as molecular data. 22.2% of the tumor cohort presented with a VISTA expression on TILs. These patients demonstrated an improved median overall survival compared to patients without VISTA expression (202.2 months vs. 21.6 months; p < 0.0001). The favorable outcome of VISTA positive tumors is significant in the entire cohort but mainly driven by the general better prognosis of T1/T2 tumors. However, in the pT1/2 group, VISTA positive tumors show a tremendous survival benefit compared to VISTA negative tumors revealing real long-term survivors in this particular subgroup. The survival difference is independent of the T-stage. This unique characteristic could influence neoadjuvant therapy concepts for EAC, since a profit of therapy could be reduced in the already favorable subgroup of VISTA positive tumors. VISTA emerges as a prognostic biomarker for longterm survival especially in the group of early TNM-stages. Future studies have to show the relevance of VISTA positive TILs within a tumor concerning response to specific immune checkpoint inhibition.

Expression and clinical significance of PD-L1, B7-H3, B7-H4 and VISTA in craniopharyngioma

“…Besides, Altan et al 33 have described that the high B7-H3 protein level (top 10 percentile) was associated with poor OS in NSCLC. Loeser et al 34 have also found that esophageal adenocarcinoma patients with VISTA expression have demonstrated an improved median OS compared with the patients without VISTA expression (202.2 months vs 21.6 months; p<0.0001). In our study, we identified that patients with high expression of VISTA had longer OS and FPS, while the expression of PD-L1, B7-H3 and B7-H4 was not related to prognosis in CPs.…”

Prognostic value of VISTA in solid tumours: a systematic review and meta-analysis

“…Villarroel 6 found that high levels of VISTA correlated with better overall survival (OS) in non-small-cell lung cancer (NSCLC) than low levels of VISTA. Loeser's study 7 showed the same trend in esophageal adenocarcinoma (EAC). In contrast, Kuklinski's study 8 showed that high expression of VISTA was associated with poor disease-specific survival (DSS).…”

“…High expression of VISTA in solid tumours is associated with favourable OS. Seven studies 6,7,[11][12][13] reported the relationship between the expression of VISTA and patients' OS. We applied a fixed effect model to calculate the pooled hazard ratio (HR) and 95% confidence interval (CI) because there was no obvious heterogeneity (P = 0.564, I 2 = 0.0%).…”

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

“…Samples were considered positive for B7-H3 and B7-H4 when ≥5% of the TCs expressing these proteins at any intensity; the 5% cut-off was chosen based on a previous publication [15]. As VISTA expression on TCs and tumourassociated immune cells (TAICs) may have distinct prognostic values [16][17][18], we evaluated the expression of VISTA on these cell types separately. TCs and TAICS were each considered VISTA-positive when ≥5% of them were stained for this protein, as described in previous publications [17,18].…”