VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?

GND
14075461X
ORCID
0000-0002-5028-5062
Affiliation
Department of General, Visceral and Transplantation Surgery, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, 81377 Munich, Germany;(M.K.A.);(J.W.)
Albertsmeier, Markus;
GND
1263033237
Affiliation
Department of General, Visceral and Vascular Surgery, Friedrich-Schiller Universität Jena, 07747 Jena, Germany;
Altendorf-Hofmann, Annelore;
GND
1174829524
ORCID
0000-0003-3708-8264
Affiliation
Department of Internal Medicine III, University Hospital, Ludwig-Maximilians-Universität (LMU), 81377 Munich, Germany;(L.H.L.);(R.D.I.);(E.K.)
Lindner, Lars H.;
GND
111942012
ORCID
0000-0002-3494-6561
Affiliation
Department of Internal Medicine III, University Hospital, Ludwig-Maximilians-Universität (LMU), 81377 Munich, Germany;(L.H.L.);(R.D.I.);(E.K.)
Issels, Rolf D.;
GND
139206752
Affiliation
Department of Internal Medicine III, University Hospital, Ludwig-Maximilians-Universität (LMU), 81377 Munich, Germany;(L.H.L.);(R.D.I.);(E.K.)
Kampmann, Eric;
ORCID
0000-0002-1347-1173
Affiliation
Musculoskeletal Oncology, Department of Orthopaedic Surgery, Physical Medicine and Rehabilitation, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, 81377 Munich, Germany;
Dürr, Hans-Roland;
Affiliation
Department of General, Visceral and Transplantation Surgery, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, 81377 Munich, Germany;(M.K.A.);(J.W.)
Angele, Martin K.;
GND
129955779
Affiliation
Institute of Pathology, Ludwig-Maximilians-Universität (LMU) Munich, 81377 Munich, Germany;
Klauschen, Frederick;
Affiliation
Department of General, Visceral and Transplantation Surgery, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, 81377 Munich, Germany;(M.K.A.);(J.W.)
Werner, Jens;
Affiliation
Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA;
Jungbluth, Achim A.;
GND
125557125X
ORCID
0000-0002-1822-0197
Affiliation
Institute of Pathology, Ludwig-Maximilians-Universität (LMU) Munich, 81377 Munich, Germany;
Knösel, Thomas

Simple Summary V 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. Abstract (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.

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