Table 2.
Immunological characteristics of the main subtypes of STS.
| Subtype | Crude Incidence Rate | TMB | Molecular alterations | TLS | Immune infiltrate | PD-L1 and other CP(mRNA expression) | ||
|---|---|---|---|---|---|---|---|---|
| LMS | Uterine LMS | 0.2/100.000/y | 1.5-2.5 | Complex genomics: high number of CNAFrequent TP53, RB1, PTEN alterationNo pathognomonic alteration Molecular targets: -PIK3CA/AKT pathway -IGF-1R |
Hormone receptor: 40-70%HRD : 20% | Absent | Low CD8+ infiltrate Low TAM infiltrate compared to other SCG More TAMs than TILsHigh M2/M1 ratio |
PDL1: 50-60% LAG-3: 15% TIM-3: 10% CD47 low SIRPα low |
| Soft tissue LMS | 0.51/100.000/y | NA | ||||||
| LPS | DDLPS | 0.81/100.000/y | 1.7 | 12q13-15 amplification MDM2-CDK4 overexpression |
Present |
Inflamed tumor
High TIL density More TAMs than TILs FoxP3+ cells present CD20+ cells present |
PD-L1: 20% LAG-3: 77% TIM-3: 88% SIRPα +++ CD47 +++ |
|
| WDLPS | Lower TIL density than in DDLPS TAMs present |
|||||||
| MRLPS | 0.1/100.000/y | t (12,16) translocation SSX-SS18 fusion protein |
NA |
Immune desert
Low TIL density TAMs present: essentially M2, correlated with PI3K pathway |
PD-L1<10% SIRPα+++ |
|||
| Pleomorphic LPS | <5% LPS | Frequent TP53 and RB1 alteration No pathognomonic alteration |
Absent | Low TIL density High TAMs/TILs ratio |
PD-L1: 0% SIRPα +++ CD47 +++ |
|||
| UPS | Two molecular subtypes: - immune high - FGFR |
0.46/100.000/y | 2.5-5 | Complex genomics: high number of mutations and CNA Frequent TP53, RB1 and ATRX alterations No pathognomonic alteration Molecular targets: -PI3K/AKT pathway -RAS/MAPK pathway |
Present |
Inflamed tumor
High TIL infiltrate Clonal TCR repertoire High TAMs infiltrate More TAMs than TILs: M2>M1 Important FoxP3 contingentCD20+ cells present |
PD-L1 30-50% LAG3 72% TIM3 83% SIRPα in ~30%CD47 low |
|
| Translocation-associated sarcomas | Synovial sarcoma | 0.13/100.000/y | 1.7 | t(X;18)(p11.2;q11.2) translocation SS18:SSX fusion protein Frequent EZH2 overexpression, TP53 alteration and MDM2 amplification |
Absent |
Immune desert
Low TIL density Low TAM infiltrate |
PD-L1<10% 60% TIM-3 30% LAG-3 SIRPα low CD47 low |
|
| ASPS | <0.1/1.000.000/y | NA | t(X;17)(p11;q25), ASPSCR1-TFE3 | NA | Low TIL density High M2/M1 ratio |
SIRPα in ~30%CD47 low | ||
SCG, Sarcomas of complex genomics, TAM, tumor-associated macrophage; TIL, tumor-infiltrating lymphocyte; TLS, Tertiary lymphoid structures; CNA, Copy-number alteration; ASPS, Alveolar soft-part sarcomas; LMS, Leiomyosarcoma; WDLPS, well-differentiated liposarcoma; DDLPS, dedifferentiated liposarcoma; MRLPS, myxoid round-cell liposarcoma; pLPS, pleomorphic liposarcoma; UPS, Undifferentiated pleomorphic sarcomas; NA, not applicable.