(P 364) EVALUATION OF THE PREDICTIVE ROLE OF SYSTEMIC AND INTRATUMORAL IMMUNITY IN PATIENTS WITH LOCALIZED LIPOSARCOMAS, MYXOFIBROSARCOMAS AND UNDIFFERENTIATED PLEOMORPHIS SARCOMAS

Objective: Achieving radical surgery still remains the only chance of recovery for most patients with soft tissue sarcoma. For this reason, identifying predictive factors of relapse that can guide best therapeutic planning remains an urgent need. This study aims to evaluate the ability of systemic and intratumoral immune status to predicte a disease relapse in patients affected by well and dedifferentiated liposarcoma (WDL, DDL), myxofibrosarcoma (MFS) and undifferentiated pleomorfic sarcoma (UPS) .

Methods: Forty-six patients that received surgery for localized WDL, DDL, MFS or UPS and followed up at the IRST Istituto Romagnolo per lo Studio dei Tumori (Meldola, Italy) from 2009 to May 2023 were retrospectively included in the study. Patients with both surgical specimen samples and presurgery blood count information were included. NLR was computed as the ratio of the absolute neutrophil count to the absolute lymphocyte count, PLR was obtained by dividing the absolute platelet count by the absolute lymphocyte count, SII was calculated as platelet count × neutrophil count/lymphocyte count while lymphocyte-to-monocyte ratio (LMR) was calculated as the ratio lymphocyte/monocyte. Information on blood counts were collected within a week before surgery. Curves of relapse free survival (RFS) were calculated using the Kaplan-Meier method. FFPE samples of the surgical specimen were collected to perform an RNAsequencing and subsequent analysis by CIBERSORT to assess the amount and composition of tumor-infiltrating immune cells.

Results: Forty-six patients were included in this single-center retrospective study, including 11 WDL, 15 DDL, 8 MFS, 12 UPS. No differences were seen in terms of RFS according to age or sex of the patients. As expected patients with G1 disease had a better RFS compared to G2 and G3 ( 110 VS 66 VS 56 months, P = 0,0494) and also histologies showed a significant difference in terms of RFS ( WDL 110mo VS 79mo MFS Vs 56 mo DDL VS 53 mo UPS; P = 0,0234). Patients also had better RFS when SSI < 991 ( P < 0,0001) NLR < 2,5 (P = 0,0001), PLR < 190 (P < 0,0001), LMR ≥2,4 (P = 0,0038).[Figure 1]
Tumor infiltrating cells fraction are shown in Figure 2. The correlation between LMR and intratumoral M2 macrophages did not reach statistical significance (p 0.352) however a trend of increase in M2 macrophages was seen as the LMR decreased.
Interestingly, as shown in Figure 3, patients with naive B-cell fraction (nBC) >3.13% had worse RFS compared to patients with B-cells ≤3.13% of the total tumor-infiltrating immune cell population ( P = 0.0181). Furthermore, patients with activated dendritic cells (aDC) >1.02% had better RFS (P = 0.0222).
No intratumoral immune population reached a statistically significant correlation with the grading, however, as shown in figure 4, patients with higher histological grading seem to have a higher presence of intratumoral monocytes and M2 macrophages.

Conclusion: Our study confirms the prognostic role of intratumoral immune cells and systemic inflammatory markers.
Unlike what was shown in previous studies, the presence of high levels of activated B cells did not show a significant difference in terms of RFS while patients with high percentages of intratumoral nBC showed a worse RFS. Even more interestingly, in our study, patients with higher percentage levels of intratumoral aDCs showed better RFS, underlining the role of dendritic cells in the antitumor response.
The activity of intratumoral dendritic cells and the role of nBCs need to be investigated in subsequent studies with larger case series.
Likewise, the correlation between grading, monocytes and M2macrophages and between these and the LMR will be evaluated on a larger series to to strengthen its statistical validity.