VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Histopathology and Tissue Microarray Construction
2.3. VISTA Immunohistochemistry
2.4. TILs, CD3, PD-1 and PD-L1
2.5. Statistical Analysis
3. Results
3.1. Patients
3.2. VISTA Expression in STS and Histopathological Subtypes
3.3. VISTA Expression Is Associated with TILs, PD-1, PD-L1 and Grading
3.4. VISTA Expression and Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variation | n | % | |
Total | 213 | 100 | |
Sex | Male | 105 | 49 |
Female | 108 | 51 | |
Histological subtype | UPS | 77 | 36 |
Leiomyosarcoma | 47 | 22 | |
Synovial sarcoma | 27 | 13 | |
Dedifferentiated liposarcoma | 34 | 16 | |
Myxoid liposarcoma | 9 | 4 | |
Angiosarcoma | 8 | 4 | |
MPNST | 11 | 5 | |
Location | Extremities | 71 | 33 |
Retroperitoneal | 45 | 21 | |
Abdominal/visceral | 35 | 17 | |
Trunk | 55 | 26 | |
Other | 7 | 3 | |
Grading | Intermediate (G2) | 102 | 48 |
High (G3) | 111 | 52 | |
Size | <50 mm | 17 | 8 |
50–79 mm | 48 | 22 | |
80–120 mm | 62 | 29 | |
>120 mm | 63 | 30 | |
Missing | 23 | 11 | |
Primary tumour/ recurrence | Primary tumour | 195 | 92 |
Recurrence | 18 | 8 | |
Metastatic disease | M0 | 195 | 92 |
M1 | 18 | 8 | |
Surgical margins | R0/R1 | 186 | 87 |
R2 or no resection | 27 | 13 | |
Radiotherapy | Done | 168 | 79 |
Not done | 45 | 21 | |
Regional hyperthermia | Done | 164 | 77 |
Not done | 49 | 23 | |
Chemotherapy | Neoadjuvant/perioperative | 213 | 100 |
Adjuvant only | 0 | 0 |
Variation | VISTA Expression | TILs | |||||||||||
Histological | 0 | 1 | 2 | 3 | Positive | Positive | Total | ||||||
Subtype | n | % | n | % | n | % | n | % | n | % | n | % | n |
UPS | 38 | 49% | 31 | 40% | 7 | 9% | 1 | 1% | 39 | 51% | 37 | 48% | 77 |
Leiomyosarcoma | 25 | 53% | 21 | 45% | 1 | 2% | 0 | 0% | 22 | 47% | 16 | 34% | 47 |
Synovial sarcoma | 14 | 52% | 13 | 48% | 0 | 0% | 0 | 0% | 13 | 48% | 3 | 11% | 27 |
Liposarcoma | 32 | 74% | 10 | 23% | 1 | 2% | 0 | 0% | 11 | 26% | 17 | 40% | 43 |
DDLPS | 25 | 74% | 8 | 24% | 1 | 3% | 0 | 0% | 9 | 26% | 15 | 44% | 34 |
Myxoid | 7 | 78% | 2 | 22% | 0 | 0% | 0 | 0% | 2 | 22% | 2 | 22% | 9 |
Angiosarcoma | 3 | 38% | 4 | 50% | 1 | 13% | 0 | 0% | 5 | 63% | 4 | 50% | 8 |
MPNST | 5 | 45% | 6 | 55% | 0 | 0% | 0 | 0% | 6 | 55% | 3 | 27% | 11 |
Total | 117 | 55% | 85 | 40% | 10 | 5% | 1 | 0% | 96 | 45% | 80 | 38% | 213 |
Variation | VISTA | ||||||
Total | Expression | No Expression | p | ||||
TILs | 0–5 | 133 | 52 | 39% | 81 | 61% | 0.033 |
≥ 6 | 80 | 44 | 55% | 36 | 45% | ||
Total | 213 | 96 | 45% | 117 | 55% | ||
CD3 | No expression | 34 | 9 | 26% | 25 | 74% | 0.023 |
Expression | 170 | 82 | 48% | 88 | 52% | ||
Total | 204 | 91 | 45% | 113 | 55% | ||
PD-1 | 0–3 | 145 | 58 | 40% | 87 | 60% | 0.046 |
≥ 4 | 61 | 34 | 56% | 27 | 44% | ||
Total | 206 | 92 | 45% | 114 | 55% | ||
PD-L1 | No expression | 171 | 73 | 43% | 98 | 57% | 0.031 |
Expression | 31 | 20 | 65% | 11 | 35% | ||
Total | 202 | 93 | 46% | 109 | 54% | ||
Metastasis | M0 | 195 | 85 | 44% | 110 | 56% | 0.215 |
M1 | 18 | 11 | 61% | 7 | 39% | ||
Total | 213 | 96 | 45% | 117 | 55% | ||
Location | Extremities | 73 | 37 | 51% | 36 | 49% | 0.249 |
Non-extremities | 140 | 59 | 42% | 81 | 58% | ||
Total | 213 | 96 | 45% | 117 | 55% | ||
Grade | Intermediate | 102 | 37 | 36% | 65 | 64% | 0.019 |
High | 111 | 59 | 53% | 52 | 47% | ||
Total | 213 | 96 | 45% | 117 | 55% |
Variation | HR (95% CI) | p-Value | |
---|---|---|---|
Age | Increase by 1 year | 1.015 (0.999–1.031) | 0.059 |
Sex | Female (vs. male) | 0.800 (0.525–1.218) | 0.298 |
VISTA | No expression (vs. expression) | 1.014 (1.014–2.363) | 0.043 |
TILs | ≥6 (vs. 0–5) | 1.125 (0.726–1.743) | 0.597 |
CD3 | No expression (vs. expression) | 0.982 (0.525–1.838) | 0.956 |
PD-1 | ≥4 (vs. 0–3) | 1.104 (0.696–1.750) | 0.674 |
PD-L1 | No expression (vs. expression) | 0.890 (0.488–1.622) | 0.703 |
Size | ≥8 cm (vs. <8 cm) | 1.358 (0.866–2.129) | 0.183 |
Metastasis | M1 (vs. M0) | 1.986 (1.008–3.912) | 0.047 |
Grade | Grade 1/2 (vs. Grade 3) | 1.446 (0.937–2.231) | 0.095 |
Surgical outcome | R2/not resected (vs. R0/1) | 5.936 (3.390–10.393) | <0.001 |
Histotype | UPS (Reference) | 0.075 | |
Leiomyosarcoma | 1.246 (0.727–2.135) | 0.424 | |
Synovial sarcoma | 1.012 (0.474–2.159) | 0.975 | |
Liposarcoma | 0.800 (0.450–1.423) | 0.447 | |
Angiosarcoma | 3.992 (1.099–14.497) | 0.035 | |
MPNST | 2.461 (1.010–5.995) | 0.047 |
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Albertsmeier, M.; Altendorf-Hofmann, A.; Lindner, L.H.; Issels, R.D.; Kampmann, E.; Dürr, H.-R.; Angele, M.K.; Klauschen, F.; Werner, J.; Jungbluth, A.A.; et al. VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy? Cancers 2022, 14, 1006. https://doi.org/10.3390/cancers14041006
Albertsmeier M, Altendorf-Hofmann A, Lindner LH, Issels RD, Kampmann E, Dürr H-R, Angele MK, Klauschen F, Werner J, Jungbluth AA, et al. VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy? Cancers. 2022; 14(4):1006. https://doi.org/10.3390/cancers14041006
Chicago/Turabian StyleAlbertsmeier, Markus, Annelore Altendorf-Hofmann, Lars H. Lindner, Rolf D. Issels, Eric Kampmann, Hans-Roland Dürr, Martin K. Angele, Frederick Klauschen, Jens Werner, Achim A. Jungbluth, and et al. 2022. "VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?" Cancers 14, no. 4: 1006. https://doi.org/10.3390/cancers14041006