Abstract
Simple SummaryV domain immunoglobulin suppressor of T cell activation (VISTA) has recently been described as a protein expressed on immune cells and tumour cells and a possible target for immunotherapy. We show for the first time that VISTA is broadly expressed across subtypes of soft tissue sarcoma. We found VISTA related to other immunopathological parameters such as tumour-infiltrating lymphocytes and observed improved survival in patients with non-T-cell-inflamed tumours expressing VISTA. Our research supports the notion of VISTA as a potential target for immunotherapy in soft tissue sarcoma.(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2, p = 0.019), higher TIL counts (p = 0.033), expression of PD1 (p = 0.046), PDL1 (p = 0.031), and CD3+ (p = 0.023). In patients without CD3+ TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (p = 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (p = 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA+ tumours show improved survival. These results may help define future immunotherapeutic approaches in STS.
Highlights
Malignant soft tissue sarcomas (STS) are a group of more than 100 rare but histopathologically distinct tumours
In 43 patients for whom tissues samples from both a preoperative biopsy and the surgical specimen were available, we found no difference in VISTA expression before and after neoadjuvant chemotherapy (p = 0.251; related-sample Friedman’s two-way analysis of variance on ranks)
Preoperative chemotherapy and regional hyperthermia may have confounded our results [14], we found no difference in VISTA expression before and after surgery
Summary
Malignant soft tissue sarcomas (STS) are a group of more than 100 rare but histopathologically distinct tumours. Originating from mesenchymal tissue, their clinical behaviour ranges from slow growth in grade 1 liposarcoma to local aggressiveness with high recurrence rates in undifferentiated pleomorphic sarcoma or frequent distant metastases in leiomyosarcoma. We regularly apply systemic therapy in high-risk, recurrent, and metastatic patients. The choice of treatment is sometimes difficult due to a paucity of specific recommendations [1,2], and the prognosis of advanced cases remains limited. Following advances in other cancers and the identification of potential targets in STS, different immunotherapeutic approaches have been proposed, including immune checkpoint inhibition, adoptive cell transfer, and tumour vaccinations [3,4]. The efficacy of such strategies was often found to be limited, and novel approaches need to be investigated [5]
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